The Protective Effect of Hard Water on Ulcerative Colitis and Crohn's Disease: A Cross-Sectional and Cohort Study of 481,468 Participants in the UK Biobank

The Protective Effect of Hard Water on Ulcerative Colitis and Crohn's Disease: A Cross-Sectional and Cohort Study of 481,468 Participants in the UK Biobank | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Protective Effect of Hard Water on Ulcerative Colitis and Crohn's Disease: A Cross-Sectional and Cohort Study of 481,468 Participants in the UK Biobank Kexin Ye, Tianyu Zhou, Zhenhe Jin, Wenxi Jiang, Zhaoxue Liu, Linwen Luo, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5552821/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Environmental factors play a significant role in the pathogenesis of inflammatory bowel disease. This study aims to investigate the association between water hardness and both the prevalence and incidence of Crohn’s disease and ulcerative colitis. Methods Cross-sectional study and cohort study were respectively conducted based on 481,468 participants in the UK Biobank. Multivariate logistics regression and Cox proportional hazards regression were used to evaluate the association between water hardness and Crohn’s disease and ulcerative colitis. Results A total of 481,468 participants were included in the cross-sectional study. Increased water hardness was correlated with reduced prevalence of Crohn’s disease (OR = 0.88, 95% CI: 0.79-0.99, p = 0.027, and p = 0.039 for the trend) and ulcerative colitis (OR = 0.83, 95% CI: 0.77-0.89, p < 0.001, and p < 0.001 for the trend). A total of 475,895 participants with the mean follow-up of 14.6 years were included in the cohort study. During the follow-up period, 1033 developed Crohn’s disease and 2165 developed ulcerative colitis. Increased water hardness was significantly associated with a decreased risk of Crohn’s disease (HR = 0.84, 95% CI: 0.73-0.97, p = 0.016, and p = 0.007 for the trend) but not ulcerative colitis. We also found that the protective effect of very hard water is more significant for individuals with low genetic risk for Crohn’s disease (HR = 0.74, 95% CI: 0.57-0.95, p = 0.019). Conclusion Higher water hardness is associated with a decreased prevalence of both Crohn’s disease and ulcerative colitis, as well as a reduced incidence of Crohn’s disease. However, no significant association was observed with the incidence of ulcerative colitis. Inflammatory bowel disease water hardness cohort study cross-sectional study Figures Figure 1 Background Inflammatory bowel diseases (IBD) are a type of chronic gastrointestinal inflammatory diseases including Crohn’s disease (CD) and ulcerative colitis (UC).[1, 2] Until 2017, the global prevalence of IBD rose to 84.3 per 100,000 people.[1] Notably, the UK recorded the second highest prevalence, with 449.6 cases per 100,000 population.[1] Inflammatory bowel diseases could be driven by a combination of genetic and environment factors, although the precise mechanism remained largely unknown.[1–3] The rapid rise in IBD incidence over the decades is closely linked to lifestyle westernization and urbanization.[4] Environmental factors include behaviors that increase individual risk (such as diet, medicine use, smoking) and broader influences that affect populations across regions (such as air pollution, and sun exposure).[5, 6] These external factors may impact disease risk and progression by influencing gut microbiota composition and immune system balance.[7] Previous studies have evaluated the correction between several environmental factors and the incidence of IBD.[4, 8] Hard water, which is rich in calcium and magnesium, forms as minerals dissolve when water passes through sedimentary rocks.[9, 10] The main minerals in hard water are calcium, present as calcite and dolomite.[9] Hard water is considered as an important source of calcium and magnesium.[10] Calcium and magnesium are essential for various biological and physiological functions, which may influence the pathophysiology of IBD development.[11] Protective effects of dietary calcium intake on IBD have been illustrated.[11] A few studies have evaluated the correlation between water supply characteristics and the IBD risk.[12, 13] For example, in a study conducted in Norway, the water supply was analyzed for physical property, iron concentration, aluminum, microbe content.[12] Another study in Iran found that exposure to iron in drinking water may have a protective effect against the development of UC.[13] However, the impact of calcium in the water supply on the risk of IBD remains unexplored. In this study, we aimed to elucidate the associations between water hardness and the prevalence and incidence risk of IBD, with a particular focus on potential interactions with genetic susceptibility. We conducted a large-scale population-based cross-sectional and cohort study within the UK biobank, incorporating polygenic risk scores (PRSs) to assess potential interactions with genetic risk. Methods Study population The current cross-sectional and cohort study is based on the UK Biobank, a large, population-based cohort comprising over 500,000 participants, aged 40 to 69, recruited across the UK between 2006 and 2010.[14] Detailed information about UK Biobank have already been described elsewhere.[14] In the current cross-sectional study, participants with missing genetic information (n=16,227) and missing water hardness information (n=4478) were excluded. Participants with unclear diagnosis information of IBD were further excluded in IBD subtype analyses (n=20). Finally, 481,468 participants were included in the cross-sectional study. For the cohort study, participants with missing genetic information (n=16,227), missing water hardness information (n=4478), and IBD diagnosis at baseline (n=5573) were excluded. Participants with unclear diagnosis information of IBD were also excluded in IBD subtype analyses (n=11). Finally, 475,895 participants were included in the cohort study. (Figure 1) Exposure and outcome measurement Domestic water hardness data were obtained from information provided by local water supply companies across England, Scotland, and Wales. For each participant visit, postcodes were approximated to the nearest kilometer to link participants to surveyed water hardness data. These data were initially provided by the University of Melbourne[9] and subsequently made available by the UK Biobank. Baseline water hardness data were derived from survey results for 2005. Data on domestic water hardness, encompassing the United States Geological Survey (USGS) classification and the World Health Organization (WHO) classification, CaCO 3 (mg/L), calcium (mg/L), and magnesium (mg/L) concentrations were included in the analysis. USGS classification categorizes water hardness into four levels according to CaCO 3 concentration: soft water (0–60 mg=L), moderately hard water (>60–120 mg=L), hard water (>120–180 mg=L), and very hard water (>180 mg=L).[9] In contrast, the WHO classifies water as soft if CaCO 3 concentration is below 200 mg/L, and as hard if it exceeds or is equal to 200 mg/L.[9] Diagnostic data were collected from both primary care and hospital inpatient records. The primary outcomes of this study were the prevalence and incidence of CD and UC, which were identified using the relevant International Classification of Diseases codes (ICD-9: 555, 556; ICD-10: K50, K51). In the cohort analysis, participants without IBD were monitored from baseline (2006–2010) until the occurrence of one of the following events: diagnosis of CD or UC, date of death, date of loss to follow-up, or the last follow-up date. Covariate assessment Data on recruitment age, ethnicity (white versus others), smoking (ever versus never), alcohol consumption (daily or almost daily, three or four times a week, one to four times a week, one to three times a month, never or special occasions only), IPAQ physical activity (International Physical Activity Questionnaire[15] with three levels: high, moderate, low) were collected from self-completed questionnaire at assessment center. Body mass index (BMI) was calculated using height and weight measurements obtained from physical assessments. The Townsend Deprivation Index (TDI) was calculated based on factors including employment, car ownership, home ownership, and household overcrowding.[16] The Charlson Comorbidity Index (CCI) was constructed using 17 comorbidities, each assigned a specific weight, linked to ICD codes from hospital inpatient data.[17] (Supplementary Table S21). Diet quality scores were construction from touchscreen food frequency questionnaire completed at assessment center based on the following 10 food items: vegetables, fruits, fish, dairy, whole grains, vegetable oils, refined grains, processed meats, unprocessed red meats, and sugar-sweetened beverages.[18] A higher diet quality scores indicates a better diet quality. Information on genetic sex was obtained from genomics data. Continuous covariates including diet quality scores, BMI, TDI were analyzed in quantiles and missing data were categorized as “unknown”. Missing categorical covariates were categorized as "unknown" for analysis. PRS scores for UC and CD were computed using a Bayesian method applied to meta-analyzed GWAS summary statistics and have been made available through the UK Biobank. Detailed methods for the development of these PRS scores are described elsewhere.[19] Adjustments were also made using the first five principal components derived from ancestry genetic data to control for population stratification. Statistical analyses In the cross-sectional study, multivariable logistic regression models were used to access the association between water hardness and the prevalence of UC, CD and IBD (UC and CD combined). In the cohort study, Cox proportional hazard regression models were used to evaluate the effect of water hardness on the incident risk of UC, CD and IBD. Odds ratios (ORs) or Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Model 1 was adjusted for age and sex. Model 2 included additional adjustments for CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI and diet quality scores. Model 3 was further adjusted for the first five principal components of ancestry genetics and PRS scores for UC and CD separately in subtype analysis. Subgroup analyses were conducted base on age, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI, PRS and diet quality scores. The interactions between water hardness and each variable were assessed using a multiplicative interaction model. Sensitivity analyses were conducted: (1) reanalyzed missing values using multiple imputation (R package mice)[20]; (2) included additional adjustments for C reactive protein, residential area, waist circumference, and educational levels separately; (3) excluding participants diagnosed with IBD within the first year of follow-up; (4) replacing genetic sex by self-reported sex; (5) excluding participants with both UC and CD diagnosis during the follow-up. The baseline characteristics were evaluated in descriptive analyses. Continuous variables are presented as mean (SD), while categorical variables are presented as counts (percentage). Results of Cox proportional hazard regression models and multivariable logistic regression models were presented as Hazard ratios (HRs) or Odds ratios (ORs) and 95% confidence intervals (CIs). A two-tailed p < 0.05 was considered as statistically significant. Statistical analyses were performed using R 4.2.2. Ethical statement The UK Biobank received ethical approval from the North West-Haydock Research Ethics Committee (REC reference: 16/NW/0274). Informed consent was obtained from all participants at the time of recruitment. Results Baseline characteristics of participants in the cross-sectional study. Baseline characteristics of participants in the cross-sectional study were presented according to the IBD diagnosis status. (Table 1) A total of 481,468 participants were included in the study, among whom 5,573 were diagnosed with IBD, including 3,750 with UC and 1,803 with CD. The mean age was 56.57 years for non-IBD participants and 57.31 years for those with IBD. Among non-IBD participants, 54.3% were female, compared to 52.1% among IBD participants. Most participants were ethnically white (94.3% for non-IBD and 95.7% for IBD). Increased water hardness was significantly associated with a decreased prevalence of CD and UC. In all three models, we found that very hard water (>180 mg/l), as classified by the USGS, significantly reduced the prevalence of UC (see Table 2 for details, Model 3: OR = 0.83, 95% CI: 0.77-0.89, p < 0.001, and p < 0.001 for the trend). This result was consistent with the classification by WHO (Model 3: OR = 0.88, 95% CI: 0.82-0.94, p < 0.001). Next, we analyzed CaCO₃ concentration as a continuous variable. The results indicated that higher CaCO₃ levels were associated with a lower prevalence of UC (Model 3: OR = 0.93, 95% CI: 0.90-0.96, p < 0.001), with consistent findings observed for Ca²⁺ concentration (Model 3: OR = 0.93, 95% CI: 0.90-0.96, p < 0.001). As for prevalent CD, significant protective effects of very hard water were found in Model 1 (OR = 0.87, 95% CI: 0.78-0.97, p = 0.011, and p = 0.016 for the trend) and Model 3 (OR = 0.88, 95% CI: 0.79-0.99, p = 0.027, and p = 0.039 for the trend). When classified according to the WHO classification, the effect was only observed in Model 1 (OR = 0.90, 95% CI: 0.82-0.99, p = 0.029). Results remained significant when analyzed continuous Ca²⁺ concentration in all three models and CaCO₃ concentration in Model 1 and Model 3. When analyzing the overall prevalence of IBD, the protective effect of hard water was consistent with the results observed in the separate analyses for UC and CD (Supplementary Table S1). Baseline characteristics of participants in the cohort study. In the cohort study, a total of 475,895 participants were included, among whom 3,212 participants were diagnosed with IBD (1,035 CD and 2,166 UC) during the mean follow-up of 14.56 years. The mean age was 56.56 years for non-IBD participants and 57.27 years for those with IBD. A slightly higher proportion of male participants were diagnosed with IBD (50.1%). Detailed characteristics were showed in Table 3. Increased water hardness was significantly associated with a decreased risk of CD but not UC. In the cohort study, hard water (120-180 mg/l) and very hard water (>180 mg/l), as classified by USGS, were found to be significantly associated with a reduced risk of incident CD in all three models (see Table 4 for details, Model 3: HR = 0.84, 95% CI: 0.73-0.97, p = 0.016, and p = 0.007 for the trend). When analyzing CaCO₃ concentration as a continuous variable, each SD increase in concentration was also significantly associated with a reduced incidence of CD in three models (Model 3: HR = 0.93, 95% CI: 0.87-0.99, p = 0.017). However, when analyzed according to the WHO classification, the results were not significant (see Table 4). Similarly, analyzing Ca²⁺ concentration as a continuous variable did not show a significant association (see Table 4). While analyzing the overall incidence of IBD, very hard water classified by the USGS (Model 3: HR =0.92, 95% CI: 0.84-1.00, p = 0.040, and p = 0.025 for the trend), hard water classified by WHO (HR = 0.92, 95% CI: 0.85-0.99, p = 0.021), and continuous CaCO₃ concentration (HR = 0.96, 95% CI: 0.92-0.99, p = 0.014) all showed significant protective effects (Supplementary Table S2). However, when UC was analyzed separately, these associations were no longer significant (see Table 4). The protective effect of hard water is more significant for individuals with low genetic risk for CD. We further evaluated the protective effect of hard water on the incident CD stratified by genetic risk. The results revealed more significant protective effects of hard water (HR = 0.35, 95% CI: 0.17-0.70, p = 0.003) and very hard water (HR = 0.74, 95% CI: 0.57-0.95, p = 0.019), as categorized by the USGS, among individuals with a low genetic risk for CD compared with the high genetic group (see Table 5). Nonetheless, the protective effect of hard water was also validated in the high genetic risk group (HR = 0.66, 95% CI: 0.45-0.97, p = 0.035). When analyzing CaCO₃ concentration within subgroups, a significant association was observed only among low genetic risk group for CD (HR = 0.88, 95% CI: 0.79-0.99, p = 0.032). The combined analysis of water hardness and CD genetic risk showed no significant interaction in reducing CD incidence (all p-interaction > 0.05). Subgroup and sensitivity analyses In the subgroup analysis, the association between water hardness and the risk of CD and UC was further examined, stratifying by factors such as age, CCI scores, BMI, IPAQ physical activity levels, alcohol consumption, smoking status, ethnicity, TDI, and diet quality scores (Supplementary Table S3-S12) Overall, stronger protective effects of water hardness on risk of CD were observed in the low-to-moderate IPAQ physical activity group, the group with alcohol consumption below weekly frequency, and among smokers. Although hard water showed no effect on the overall risk of UC, subgroup analysis revealed a protective effect among male, individuals with low-to-moderate physical activity, and non-smokers. In sensitivity analyses, we obtained consistent results when using multiple imputation to handle covariates, excluding participants diagnosed within the first year of follow-up, and excluding participants with both UC and CD diagnoses. Additionally, similar findings were observed when further adjusting for C-reactive protein, residential area, waist circumference, and educational level as covariates. Results remained comparable when using self-reported sex instead of genetic sex. (Supplementary Table S13-S20) Discussion In this large-scale population-based cross-sectional and cohort study consisting of 481,468 participants in the UK Biobank, our findings indicate that hard water is associated with a reduced prevalence of IBD. Additionally, we report the association between hard water and a decreased incidence of CD in participants without IBD at baseline. However, water hardness did not influence UC incidence. Consistently, an increase in CaCO₃ concentration was associated with a reduction in IBD prevalence and CD incidence, whereas no association was found between magnesium concentrations and IBD. The protective effect on CD risk is more pronounced among individuals with low genetic susceptibility. Besides, results also varied across different physical activity, alcohol consumption and smoking status subgroups. Although previous research has shown that calcium intake may have protective benefits for IBD, the relationship between water hardness and IBD remains unexplored.[11, 21] A previous case-controlled study showed that higher dietary calcium intake was correlated with a reduced prevalence of UC.[21] Another cohort study revealed that participants consuming milk have significantly lower risk of developing CD.[11] However, the underlying mechanisms have not been fully understood. Calcium is the most prevalent cation in the human body and acts as a ubiquitous second messenger, influencing various cellular functions such as differentiation, apoptosis, and proliferation.[22] Calcium are also closely related to barrier permeability and immune response.[23] The regulatory role of calcium ions at the cellular level in IBD has been well-documented, and dietary calcium intake has also been shown to alleviate colitis in mouse models via the TNF-α pathway.[24] In the meanwhile, calcium supplementation could modulate gut microbiota, which might be a potential mechanism underlying its beneficial effects on IBD.[25] While previous research has suggested that magnesium may alleviate colitis and improve intestinal barrier function,[26] our study did not find significant associations between water magnesium concentrations and the prevalence or incidence of IBD. Water is a fundamental necessity for life. The associations between water quality and health-related outcomes carry significant public health implications.[27] Earlier research has examined the impact of water hardness on different health conditions.[9, 10, 28] A large-scale study examining water hardness and both all-cause and cause-specific cancers found that hard water has a protective effect against several types of cancer, including gastrointestinal cancers such as esophageal, stomach, and colorectal cancers.[10] Another study based on the UK Biobank revealed the association between water hardness and eczema.[9] Several studies have focused on the relationship between water quality and IBD, which evaluated several metal ions and other quality index.[12, 13] A study on UK tap water suggested that the effects of water composition on health may be mediated through modulation of the gut microbiota.[29] However, evidence on the association between water hardness and IBD risk remains limited. This study is the first to identify a protective effect of hard water on both the prevalence and incidence of IBD. Although no significant interaction effect between water hardness and IBD was found, the protective effect of hard water on the risk of CD was significantly stronger in participants with lower genetic susceptibility to CD. The pathological processes of IBD are triggered by both genetic and environmental factors.[30, 31] Previous studies have identified numerous potential loci and their interactions with environmental factors.[30] Mode of diet and nutrition intake potentially interact with susceptible gene loci, regulating the course of IBD through mechanisms such as gut microbiota and immune responses.[31] Researchers also found that the impact of dietary iron intake on IBD was significantly modified by a coding variant in FcγRIIA gene, providing evidence for an environmental metal-gene interaction in the progression of IBD.[32] However, the potential interaction effect between calcium and IBD susceptible gene variants remains unclear and warrants further investigation. There are several strengths of our study. Firstly, our study is a population-based cross-sectional and cohort study with large sample size and long-term follow-up. The combination of cross-sectional and longitudinal analyses provides more comprehensive evidence to support the conclusions. Secondly, to our knowledge, this is the first study to evaluate the associations between water hardness and the prevalence and incidence of IBD. We adjusted potential confounding variables such as genetic risk, alcohol consumption and smoking status and provided robust statistical evidence. Thirdly, we have considered the influence of genetic factors on IBD risk. The interaction effect between genetics and water hardness were further analyzed. We examined how water quality impacts groups with varying levels of genetic risk differently, providing evidence for the combined influence of environmental and genetic factors in the pathogenesis of IBD. However, there are still limitations of our study. Firstly, the data we obtained from the UK Biobank pertains to the water supply of the area where participants reside. One limitation is that the actual water source of some participants may not be tap water. However, due to data availability constraints, we were unable to obtain this part of information. Secondly, other water quality data are not available in UK Biobank, such as pH, metal concentrations, which limits our further evaluations. Thirdly, because the participants in this study were primarily of White British descent, the generalizability of the conclusions to other ethnic groups is unclear. Fourthly, the participants in this study were aged 40-69, which may not fully reflect the population of individuals with an early onset of disease. Conclusion In conclusion, our study reveals the protective effects of water quality on IBD and highlights its differential impact across groups with varying genetic risk. Hard water is associated with lower prevalence of UC and CD, and reduces the risk of incident CD as well. This effect is more pronounced among participants with lower genetic risk of CD. Our findings provide valuable implications for public health strategies and disease prevention, offering important insights into the potential role of environmental factors, such as water quality, in modulating IBD risk. This highlights the importance of considering environmental factors alongside genetic susceptibility when developing preventive measures and strategies for managing IBD. Further research is needed to confirm these associations and explore the underlying mechanisms linking water quality, genetic risk, and IBD. Abbreviations BMI, Body mass index CCI, Charlson Comorbidity Index CD, Crohn’s disease GWAS, Genome-wide association study HR, Hazard ratios IBD, Inflammatory bowel diseases ICD, International Classification of Diseases IPAQ, International Physical Activity Questionnaire OR, Odds ratios PRS, Polygenic risk scores TDI, Townsend Deprivation Index UC, Ulcerative colitis USGS, United States Geological Survey WHO, World Health Organization 95% CI, 95% Confidence intervals Declarations Ethics approval and consent to participate The UK Biobank received ethical approval from the North West-Haydock Research Ethics Committee (REC reference: 16/NW/0274). Informed consent was obtained from all participants at the time of recruitment. Consent for publication Not applicable. Availability of data and materials All data analyzed during this study are included in this article and its supplementary information files. Competing interests The authors declare that they have no competing interests. Funding This study was funded by High-Level Talent Science and Technology Innovation Leading Talent Program of Zhejiang Province, reference number: 2023R5239. Authors' contributions Kexin Ye: data processing, data analysis, table editing, original draft writing. Tianyu Zhou, Zhenhe Jin: methodology, data processing, manuscript editing. Wenxi Jiang, Zhaoxue Liu: methodology, manuscript editing. Linwen Luo, Yize Wang: table editing, manuscript editing. Zhe Shen: supervision, funding acquisition, conceptualization, project administration. Acknowledgements This study was conducted under the application number of 176969 of UK Biobank. We sincerely acknowledge the contributions of the participants and the UK Biobank team. References Zhao M, Gönczi L, Lakatos PL, Burisch J. The Burden of Inflammatory Bowel Disease in Europe in 2020. J Crohns Colitis. 2021;15:1573–87. Adolph TE, Meyer M, Schwärzler J, Mayr L, Grabherr F, Tilg H. The metabolic nature of inflammatory bowel diseases. 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Bowyer RCE, Schillereff DN, Jackson MA, Le Roy C, Wells PM, Spector TD, et al. Associations between UK tap water and gut microbiota composition suggest the gut microbiome as a potential mediator of health differences linked to water quality. Sci Total Environ. 2020;739:139697. Graham DB, Xavier RJ. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature. 2020;578:527–39. Noble AJ, Nowak JK, Adams AT, Uhlig HH, Satsangi J. Defining Interactions Between the Genome, Epigenome, and the Environment in Inflammatory Bowel Disease: Progress and Prospects. Gastroenterology. 2023;165:44-60.e2. Khalili H, de Silva PS, Ananthakrishnan AN, Lochhead P, Joshi A, Garber JJ, et al. Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohn’s Disease and Ulcerative Colitis. Inflamm Bowel Dis. 2017;23:1088–95. Tables Table 1. Characteristics of participants according to IBD status and subtype in the cross-sectional study Non-IBD IBD CD UC (n=475895) (n=5573) (n=1803) (n=3750) Age, mean (SD) 56.57 (8.08) 57.31 (7.9) 56.69 (8.06) 57.61 (7.81) Genetic sex, n (%) Female 258383 (54.3) 2903 (52.1) 998 (55.4) 1895 (50.5) Male 217512 (45.7) 2670 (47.9) 805 (44.6) 1855 (49.5) Ethnicity, n (%) White 448558 (94.3) 5334 (95.7) 1725 (95.7) 3589 (95.7) Others 26849 (5.6) 233 (4.2) 76 (4.2) 157 (4.2) Unknown 488 (0.1) 6 (0.1) 2 (0.1) 4 (0.1) Education levels, n (%) College or university 154180 (32.4) 1557 (27.9) 467 (25.9) 1086 (29) Others 321223 (67.5) 4010 (72.0) 1334 (74) 2660 (70.9) Unknown 492 (0.1) 6 (0.1) 2 (0.1) 4 (0.1) Townsend deprivation index, mean (SD) -1.3 (3.09) -1.26 (3.08) -1.08 (3.19) -1.35 (3.03) BMI, mean (SD) 27.44 (4.8) 27.15 (4.68) 26.84 (4.8) 27.3 (4.61) Diet Score, mean (SD) 49.57 (14.91) 46.82 (15.4) 44.76 (15.83) 47.82 (15.1) Charlson Comorbidity Index, mean (SD) 0.22 (0.7) 0.36 (0.92) 0.38 (0.95) 0.38 (0.96) IPAQ activity, n (%) High 150314 (31.6) 1629 (29.2) 503 (27.9) 1120 (29.9) Moderate 149592 (31.4) 1674 (30) 519 (28.8) 1151 (30.7) Low 68027 (14.3) 907 (16.3) 319 (17.7) 586 (15.6) Unknown 107962 (22.7) 1363 (24.5) 462 (25.6) 893 (23.8) Alcohol, n (%) Daily or almost daily 96867 (20.4) 1028 (18.4) 285 (15.8) 741 (19.8) Three or four times a week 109971 (23.1) 1185 (21.3) 356 (19.7) 820 (21.9) One to four times a week 122608 (25.8) 1389 (24.9) 449 (24.9) 939 (25) One to three times a month 52814 (11.1) 663 (11.9) 234 (13) 427 (11.4) Never or special occasions only 92590 (19.5) 1297 (23.3) 476 (26.4) 815 (21.7) Unknown 1045 (0.2) 11 (0.2) 3 (0.2) 8 (0.2) Smoking, n (%) Ever 282980 (59.5) 3584 (64.3) 1186 (65.8) 2385 (63.6) Never 190538 (40) 1967 (35.3) 610 (33.8) 1350 (36) Not know 2377 (0.5) 22 (0.4) 7 (0.4) 15 (0.4) Water hardness (USGS), n (%) 0-60 169376 (35.6) 2163 (38.8) 695 (38.5) 1459 (38.9) 60-120 94420 (19.9) 1115 (20) 347 (19.2) 762 (20.3) 120-180 28236 (5.9) 342 (6.1) 107 (5.9) 232 (6.2) >180 183530 (38.6) 1951 (35) 654 (36.3) 1295 (34.6) Water hardness (WHO), n (%) <200 294657 (62) 3655 (65.6) 1163 (64.5) 2474 (66) ≥200 180905 (38) 1916 (34.4) 640 (35.5) 1274 (34) CaCO 3 concentration, mean (SD) 146.19 (114.98) 136.69 (112.12) 137.64 (113.03) 135.7 (111.71) Ca concentration, mean (SD) 51.3 (40.03) 48.28 (39.15) 47.99 (39.22) 48.45 (39.21) Mg concentration, mean (SD) 4.6 (3.76) 4.57 (3.8) 4.55 (3.72) 4.57 (3.81) Abbreviations: BMI, Body mass index; IPAQ, International Physical Activity Questionnaire; USGS, United States Geological Survey; WHO, World Health Organization. Table 2. Association between water hardness and prevalent UC and CD in the cross-sectional study CD UC Cases Model 1 OR (95% CI) P Model 2 OR (95% CI) P Model 3 OR (95% CI) P Cases Model 1 OR (95% CI) P Model 2 OR (95% CI) P Model 3 OR (95% CI) P Water hardness (USGS, mg/l) 0-60 695 ref ref ref 1459 ref ref ref 60-120 347 0.90 (0.79-1.02) 0.096 0.91 (0.80-1.04) 0.158 0.91 (0.80-1.04) 0.151 762 0.93 (0.86-1.02) 0.130 0.94 (0.86-1.02) 0.153 0.95 (0.87-1.04) 0.236 120-180 107 0.92 (0.75-1.13) 0.450 0.96 (0.78-1.18) 0.683 0.95 (0.77-1.17) 0.620 232 0.96 (0.84-1.11) 0.583 0.97 (0.85-1.12) 0.694 0.98 (0.85-1.13) 0.797 >180 654 0.87 (0.78-0.97) 0.011 0.90 (0.81-1.00) 0.058 0.88 (0.79-0.99) 0.027 1295 0.83 (0.77-0.89) <0.001 0.84 (0.78-0.91) <0.001 0.86 (0.80-0.93) <0.001 P for trend 0.016 0.081 0.039 <0.001 <0.001 <0.001 Water hardness (WHO, mg/l) <200 1163 ref ref ref 2474 ref ref ref ≥200 640 0.90 (0.82-0.99) 0.029 0.92 (0.83-1.02) 0.098 0.90 (0.82-1.00) 0.048 1274 0.85 (0.79-0.91) <0.001 0.86 (0.80-0.92) <0.001 0.88 (0.82-0.94) <0.001 CaCO 3 concentration (per SD) 0.94 (0.89-0.98) 0.007 0.95 (0.91-1.00) 0.041 0.94 (0.90-0.99) 0.017 0.92 (0.89-0.95) <0.001 0.92 (0.89-0.96) <0.001 0.93 (0.90-0.96) <0.001 Ca concentration (per SD) 0.92 (0.88-0.97) 0.001 0.93 (0.89-0.98) 0.008 0.93 (0.88-0.97) 0.002 0.93 (0.90-0.97) <0.001 0.94 (0.91-0.98) <0.001 0.95 (0.92-0.98) 0.003 Mg concentration (per SD) 0.99 (0.95-1.04) 0.814 1.00 (0.95-1.05) 0.985 1.00 (0.95-1.05) 0.918 0.99 (0.96-1.03) 0.624 0.99 (0.96-1.03) 0.626 1.00 (0.96-1.03) 0.895 Abbreviations: USGS, United States Geological Survey; WHO, World Health Organization. Model 1: adjusted for age and sex; Model 2: adjusted for age, sex, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI and diet quality scores; Model 3: adjusted for age, sex, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI, diet quality scores, the first five principal components of ancestry genetics and PRS scores. Table 3. Characteristics of participants according to IBD status and subtype in the cohort study Non-IBD IBD CD UC (n=472683) (n=3212) (n=1035) (n=2166) Age, mean (SD) 56.56 (8.08) 57.27 (8.01) 56.97 (8.25) 57.42 (7.88) Genetic sex, n (%) Female 256779 (54.3) 1598 (49.9) 561 (54.2) 1037 (47.9) Male 215904 (45.7) 1603 (50.1) 474 (45.8) 1129 (52.1) Ethnicity, n (%) White 445543 (94.3) 3005 (93.9) 976 (94.3) 2029 (93.7) Others 26656 (5.6) 192 (6) 58 (5.6) 134 (6.2) Unknown 484 (0.1) 4 (0.1) 1 (0.1) 3 (0.1) Education levels, n (%) College or university 153372 (32.4) 807 (25.2) 266 (25.7) 541 (25) Others 318823 (67.4) 2390 (74.7) 768 (74.2) 1622 (74.9) Unknown 488 (0.1) 4 (0.1) 1 (0.1) 3 (0.1) Townsend deprivation index, mean (SD) -1.31 (3.09) -0.89 (3.25) -0.71 (3.26) -0.97 (3.25) BMI, mean (SD) 27.43 (4.8) 27.98 (5.06) 28.08 (5.22) 27.93 (4.97) Diet Score, mean (SD) 49.59 (14.91) 47.89 (15.27) 47.18 (15.22) 48.22 (15.29) Charlson Comorbidity Index, mean (SD) 0.22 (0.73) 0.33 (0.86) 0.33 (0.81) 0.34 (0.89) IPAQ activity, n (%) High 149363 (31.6) 947 (29.6) 287 (27.7) 660 (30.5) Moderate 148657 (31.4) 931 (29.1) 320 (30.9) 611 (28.2) Low 67547 (14.3) 479 (15) 156 (15.1) 323 (14.9) Unknown 107116 (22.7) 844 (26.4) 272 (26.3) 572 (26.4) Alcohol, n (%) Daily or almost daily 96205 (20.4) 661 (20.6) 200 (19.3) 461 (21.3) Three or four times a week 109344 (23.1) 625 (19.5) 195 (18.8) 430 (19.9) One to four times a week 121809 (25.8) 794 (24.8) 242 (23.4) 552 (25.5) One to three times a month 52468 (11.1) 346 (10.8) 120 (11.6) 226 (10.4) Never or special occasions only 91821 (19.4) 766 (23.9) 276 (26.7) 490 (22.6) Unknown 1036 (0.2) 9 (0.3) 2 (0.2) 7 (0.3) Smoking, n (%) Ever 280777 (59.4) 2194 (68.5) 705 (68.1) 1489 (68.7) Never 189545 (40.1) 991 (31) 328 (31.7) 663 (30.6) Unknown 2361 (0.5) 16 (0.5) 2 (0.2) 14 (0.6) Water hardness (USGS), n (%) 0-60 168183 (35.6) 1191 (37.2) 415 (40.2) 776 (35.8) 60-120 93755 (19.8) 661 (20.7) 206 (19.9) 455 (21) 120-180 28052 (5.9) 183 (5.7) 37 (3.6) 146 (6.7) >180 182363 (38.6) 1163 (36.4) 375 (36.3) 788 (36.4) Water hardness (WHO), n (%) <200 292598 (61.9) 2052 (64.2) 664 (64.3) 1388 (64.1) ≥200 179755 (38.1) 1146 (35.8) 369 (35.7) 777 (35.9) CaCO 3 concentration, mean (SD) 145.68 (115.08) 139.8 (112.89) 137 (113.74) 141.09 (112.48) Ca concentration, mean (SD) 51.1 (40.08) 51.02 (40.32) 49.33 (40.09) 51.79 (40.42) Mg concentration, mean (SD) 4.58 (3.76) 4.46 (3.45) 4.35 (3.32) 4.51 (3.52) Abbreviations: BMI, Body mass index; IPAQ, International Physical Activity Questionnaire; USGS, United States Geological Survey; WHO, World Health Organization. Table 4. Association between water hardness and incident UC and CD in the cohort study CD UC Cases Model 1 HR (95% CI) P Model 2 HR (95% CI) P Model 3 HR (95% CI) P Cases Model 1 HR (95% CI) P Model 2 HR (95% CI) P Model 3 HR (95% CI) P Water hardness (USGS, mg/l) 0-60 415 ref ref ref 776 ref ref ref 60-120 206 0.89 (0.75-1.05) 0.169 0.91 (0.77-1.07) 0.252 0.90 (0.76-1.07) 0.241 455 1.05 (0.93-1.18) 0.430 1.06 (0.94-1.19) 0.356 1.07 (0.95-1.20) 0.260 120-180 37 0.53 (0.38-0.75) <0.001 0.56 (0.40-0.78) <0.001 0.55 (0.39-0.77) 180 375 0.84 (0.73-0.96) 0.014 0.85 (0.74-0.98) 0.024 0.84 (0.73-0.97) 0.016 788 0.95 (0.86-1.04) 0.275 0.95 (0.85-1.04) 0.270 0.96 (0.87-1.07) 0.469 P for trend 0.007 0.012 0.007 0.258 0.262 0.452 Water hardness (WHO, mg/l) <200 664 ref ref ref 1388 ref ref ref ≥200 369 0.91 (0.8-1.03) 0.152 0.91 (0.8-1.04) 0.167 0.90 (0.79-1.03) 0.126 777 0.92 (0.84-1.01) 0.070 0.92 (0.84-1.00) 0.054 0.93 (0.85-1.02) 0.106 CaCO 3 concentration (per SD) 0.93 (0.87-0.99) 0.020 0.93 (0.87-0.99) 0.027 0.93 (0.87-0.99) 0.017 0.97 (0.93-1.01) 0.130 0.97 (0.93-1.01) 0.118 0.97 (0.93-1.02) 0.223 Ca concentration (per SD) 0.96 (0.9-1.02) 0.174 0.95 (0.89-1.02) 0.140 0.95 (0.89-1.01) 0.104 1.03 (0.98-1.07) 0.207 1.02 (0.98-1.07) 0.310 1.03 (0.98-1.07) 0.233 Mg concentration (per SD) 0.93 (0.87-1) 0.056 0.95 (0.88-1.01) 0.119 0.94 (0.88-1.01) 0.110 0.98 (0.94-1.03) 0.473 0.99 (0.95-1.04) 0.693 1.00 (0.95-1.04) 0.848 Abbreviations: USGS, United States Geological Survey; WHO, World Health Organization. Model 1: adjusted for age and sex; Model 2: adjusted for age, sex, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI and diet quality scores; Model 3: adjusted for age, sex, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI, diet quality scores, the first five principal components of ancestry genetics and PRS scores. Table 5. Association between water hardness and the risk of CD by genetic susceptibility Low genetic risk High genetic risk P for interaction HR (95% CI) P HR (95% CI) P Water hardness (USGS, mg/l) 0-60 ref ref ref 60-120 0.250 0.87 (0.65-1.16) 0.342 0.92 (0.75-1.14) 0.211 120-180 0.124 0.35 (0.17-0.70) 0.003 0.66 (0.45-0.97) 0.035 >180 0.794 0.74 (0.57-0.95) 0.019 0.89 (0.75-1.07) 0.457 P for trend 0.008 0.162 Water hardness (WHO, mg/l) <200 ref ref ref ≥200 0.427 0.83 (0.66-1.05) 0.127 0.94 (0.80-1.10) 0.446 CaCO 3 concentration (per SD) 0.348 0.88 (0.79-0.99) 0.032 0.95 (0.88-1.02) 0.171 Ca concentration (per SD) 0.272 0.90 (0.80-1.01) 0.085 0.97 (0.90-1.05) 0.462 Mg concentration (per SD) 0.655 0.02 (0.81-1.05) 0.226 0.95 (0.88-1.04) 0.285 Abbreviations: USGS, United States Geological Survey; WHO, World Health Organization. Adjusted for age, sex, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI, diet quality scores, the first five principal components of ancestry genetics. Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterials.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5552821","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":385221847,"identity":"92e1ed3c-8dc3-47e2-a4c6-b3d33b82f0e6","order_by":0,"name":"Kexin Ye","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Kexin","middleName":"","lastName":"Ye","suffix":""},{"id":385221848,"identity":"36c51bcd-4f0e-43b1-945b-43c92966e151","order_by":1,"name":"Tianyu Zhou","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Tianyu","middleName":"","lastName":"Zhou","suffix":""},{"id":385221849,"identity":"17c326b7-54c2-4f17-80bd-74a9db8dca4f","order_by":2,"name":"Zhenhe Jin","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Zhenhe","middleName":"","lastName":"Jin","suffix":""},{"id":385221850,"identity":"f7dcd1dd-9d33-489f-8c04-6372dfb70a9d","order_by":3,"name":"Wenxi Jiang","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Wenxi","middleName":"","lastName":"Jiang","suffix":""},{"id":385221851,"identity":"59831ce0-9a47-4da5-864c-275975a5c9fe","order_by":4,"name":"Zhaoxue Liu","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Zhaoxue","middleName":"","lastName":"Liu","suffix":""},{"id":385221852,"identity":"dcc0aad5-e0c0-4172-96a3-b31a3ea0b567","order_by":5,"name":"Linwen Luo","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Linwen","middleName":"","lastName":"Luo","suffix":""},{"id":385221853,"identity":"7ea2c35b-2825-4846-8840-e34b52c813e9","order_by":6,"name":"Yize Wang","email":"","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Yize","middleName":"","lastName":"Wang","suffix":""},{"id":385221854,"identity":"159cf352-41fd-49c6-945f-572cdbae5106","order_by":7,"name":"Zhe Shen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYFAC5oMPP1TYMDA2ANk8xGlhSzaWOJNGkhYeMwnetsNQNjEa5PuPJUhItp23Z56RwPjgbRuDvDkhLQYHDh8wKDh3m5lxRgKz4dw2BsOdDYS0MLYlJEiU3WYDamGT5m1jSDA4QMhhzTwGB3jYzvEAtbD/JkoLwzEewwaetgMSIFuYidJicIYtmVniTLIBY8/DZsk55yQMNxB0WP/h4z8/VNjZG7YnH/zwpsxGnrDDYMCwARyZEsSqB1lHgtpRMApGwSgYYQAA+Lw93p/G1Q8AAAAASUVORK5CYII=","orcid":"","institution":"First Affiliated Hospital Zhejiang University","correspondingAuthor":true,"prefix":"","firstName":"Zhe","middleName":"","lastName":"Shen","suffix":""}],"badges":[],"createdAt":"2024-11-30 07:08:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5552821/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5552821/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78320515,"identity":"c6e7398a-c6b6-4998-80df-1fc759a1b1a9","added_by":"auto","created_at":"2025-03-12 05:02:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":72732,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flow diagram. The flow diagram showed the design of this study.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5552821/v1/702fb4e8ec44130eaac7f6fc.png"},{"id":78322454,"identity":"9b70e8c1-0e62-4cf6-a481-7adb0e7f2d1e","added_by":"auto","created_at":"2025-03-12 05:34:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2217020,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5552821/v1/235060d7-8621-4b28-8843-c75fd3da3a7c.pdf"},{"id":78320516,"identity":"97632e5a-f808-4d53-af02-21452de46dc9","added_by":"auto","created_at":"2025-03-12 05:02:23","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":107354,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-5552821/v1/9cc2fbad80dcfd5b39ac56f9.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Protective Effect of Hard Water on Ulcerative Colitis and Crohn's Disease: A Cross-Sectional and Cohort Study of 481,468 Participants in the UK Biobank","fulltext":[{"header":"Background","content":"\u003cp\u003eInflammatory bowel diseases (IBD) are a type of chronic gastrointestinal inflammatory diseases including Crohn\u0026rsquo;s disease (CD) and ulcerative colitis (UC).[1, 2] Until 2017, the global prevalence of IBD rose to 84.3 per 100,000 people.[1] Notably, the UK recorded the second highest prevalence, with 449.6 cases per 100,000 population.[1] Inflammatory bowel diseases could be driven by a combination of genetic and environment factors, although the precise mechanism remained largely unknown.[1\u0026ndash;3] The rapid rise in IBD incidence over the decades is closely linked to lifestyle westernization and urbanization.[4] Environmental factors include behaviors that increase individual risk (such as diet, medicine use, smoking) and broader influences that affect populations across regions (such as air pollution, and sun exposure).[5, 6] These external factors may impact disease risk and progression by influencing gut microbiota composition and immune system balance.[7] Previous studies have evaluated the correction between several environmental factors and the incidence of IBD.[4, 8]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHard water, which is rich in calcium and magnesium, forms as minerals dissolve when water passes through sedimentary rocks.[9, 10] The main minerals in hard water are calcium, present as \u0026nbsp;calcite and dolomite.[9] Hard water is considered as an important source of calcium and magnesium.[10] Calcium and magnesium are essential for various biological and physiological functions, which may influence the pathophysiology of IBD development.[11] Protective effects of dietary calcium intake on IBD have been illustrated.[11] A few studies have evaluated the correlation between water supply characteristics and the IBD risk.[12, 13] For example, in a study conducted in Norway, the water supply was analyzed for physical property, iron concentration, aluminum, microbe content.[12] Another study in Iran found that exposure to iron in drinking water may have a protective effect against the development of UC.[13] However, the impact of calcium in the water supply on the risk of IBD remains unexplored. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this study, we aimed to elucidate the associations between water hardness and the prevalence and incidence risk of IBD, with a particular focus on potential interactions with genetic susceptibility. We conducted a large-scale population-based cross-sectional and cohort study within the UK biobank, incorporating polygenic risk scores (PRSs) to assess potential interactions with genetic risk.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe current cross-sectional and cohort study is based on the UK Biobank, a large, population-based cohort comprising over 500,000 participants, aged 40 to 69, recruited across the UK between 2006 and 2010.[14] Detailed information about UK Biobank have already been described elsewhere.[14]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the current cross-sectional study, participants with missing genetic information (n=16,227) and missing water hardness information (n=4478) were excluded. Participants with unclear diagnosis information of IBD were further excluded in IBD subtype analyses (n=20). Finally, 481,468 participants were included in the cross-sectional study. For the cohort study, participants with missing genetic information (n=16,227), missing water hardness information (n=4478), and IBD diagnosis at baseline (n=5573) were excluded. Participants with unclear diagnosis information of IBD were also excluded in IBD subtype analyses (n=11). Finally, 475,895 participants were included in the cohort study. (Figure 1)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eExposure and outcome measurement\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDomestic water hardness data were obtained from information provided by local water supply companies across England, Scotland, and Wales. For each participant visit, postcodes were approximated to the nearest kilometer to link participants to surveyed water hardness data. These data were initially provided by the University of Melbourne[9] and subsequently made available by the UK Biobank. Baseline water hardness data were derived from survey results for 2005.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData on domestic water hardness, encompassing the United States Geological Survey (USGS) classification and the World Health Organization (WHO) classification, CaCO\u003csub\u003e3\u003c/sub\u003e (mg/L), calcium (mg/L), and magnesium (mg/L) concentrations were included in the analysis. USGS classification categorizes water hardness into four levels according to CaCO\u003csub\u003e3\u0026nbsp;\u003c/sub\u003econcentration: soft water (0\u0026ndash;60 mg=L), moderately hard water (\u0026gt;60\u0026ndash;120 mg=L), hard water (\u0026gt;120\u0026ndash;180 mg=L), and very hard water (\u0026gt;180 mg=L).[9] In contrast, the WHO classifies water as soft if CaCO\u003csub\u003e3\u0026nbsp;\u003c/sub\u003econcentration is below 200 mg/L, and as hard if it exceeds or is equal to 200 mg/L.[9]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDiagnostic data were collected from both primary care and hospital inpatient records. The primary outcomes of this study were the prevalence and incidence of CD and UC, which were identified using the relevant International Classification of Diseases codes (ICD-9: 555, 556; ICD-10: K50, K51). In the cohort analysis, participants without IBD were monitored from baseline (2006\u0026ndash;2010) until the occurrence of one of the following events: diagnosis of CD or UC, date of death, date of loss to follow-up, or the last follow-up date.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eCovariate assessment\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eData on recruitment age, ethnicity (white versus others), smoking (ever versus never), alcohol consumption (daily or almost daily, three or four times a week, one to four times a week, one to three times a month, never or special occasions only), IPAQ physical activity (International Physical Activity Questionnaire[15] with three levels: high, moderate, low) were collected from self-completed questionnaire at assessment center. Body mass index (BMI) was calculated using height and weight measurements obtained from physical assessments. The Townsend Deprivation Index (TDI) was calculated based on factors including employment, car ownership, home ownership, and household overcrowding.[16] The Charlson Comorbidity Index (CCI) was constructed using 17 comorbidities, each assigned a specific weight, linked to ICD codes from hospital inpatient data.[17] (Supplementary Table S21). Diet quality scores were construction from touchscreen food frequency questionnaire completed at assessment center based on the following 10 food items: vegetables, fruits, fish, dairy, whole grains, vegetable oils, refined grains, processed meats, unprocessed red meats, and sugar-sweetened beverages.[18] A higher diet quality scores indicates a better diet quality. Information on genetic sex was obtained from genomics data. Continuous covariates including diet quality scores, BMI, TDI were analyzed in quantiles and missing data were categorized as \u0026ldquo;unknown\u0026rdquo;. Missing categorical covariates were categorized as \u0026quot;unknown\u0026quot; for analysis. PRS scores for UC and CD were computed using a Bayesian method applied to meta-analyzed GWAS summary statistics and have been made available through the UK Biobank. Detailed methods for the development of these PRS scores are described elsewhere.[19] Adjustments were also made using the first five principal components derived from ancestry genetic data to control for population stratification.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn the cross-sectional study, multivariable logistic regression models were used to access the association between water hardness and the prevalence of UC, CD and IBD (UC and CD combined). In the cohort study, Cox proportional hazard regression models were used to evaluate the effect of water hardness on the incident risk of UC, CD and IBD. Odds ratios (ORs) or Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Model 1 was adjusted for age and sex. Model 2 included additional adjustments for CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI and diet quality scores. Model 3 was further adjusted for the first five principal components of ancestry genetics and PRS scores for UC and CD separately in subtype analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSubgroup analyses were conducted base on age, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI, PRS and diet quality scores. The interactions between water hardness and each variable were assessed using a multiplicative interaction model. Sensitivity analyses were conducted: (1) reanalyzed missing values using multiple imputation (R package mice)[20]; (2) included additional adjustments for C reactive protein, residential area, waist circumference, and educational levels separately; (3) excluding participants diagnosed with IBD within the first year of follow-up; (4) replacing genetic sex by self-reported sex; (5) excluding participants with both UC and CD diagnosis during the follow-up.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe baseline characteristics were evaluated in descriptive analyses. Continuous variables are presented as mean (SD), while categorical variables are presented as counts (percentage). Results of Cox proportional hazard regression models and multivariable logistic regression models were presented as Hazard ratios (HRs) or Odds ratios (ORs) and 95% confidence intervals (CIs). A two-tailed p \u0026lt; 0.05 was considered as statistically significant. Statistical analyses were performed using R 4.2.2.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEthical statement\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe UK Biobank received ethical approval from the North West-Haydock Research Ethics Committee (REC reference: 16/NW/0274). Informed consent was obtained from all participants at the time of recruitment.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBaseline characteristics of participants in the cross-sectional study.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBaseline characteristics of participants in the cross-sectional study were presented according to the IBD diagnosis status. (Table 1) A total of 481,468 participants were included in the study, among whom 5,573 were diagnosed with IBD, including 3,750 with UC and 1,803 with CD. The mean age was 56.57 years for non-IBD participants and 57.31 years for those with IBD. Among non-IBD participants, 54.3% were female, compared to 52.1% among IBD participants. Most participants were ethnically white (94.3% for non-IBD and 95.7% for IBD).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eIncreased water hardness was significantly associated with a decreased prevalence of CD and UC.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn all three models, we found that very hard water (\u0026gt;180 mg/l), as classified by the USGS, significantly reduced the prevalence of UC (see Table 2 for details, Model 3: OR = 0.83, 95% CI: 0.77-0.89, p \u0026lt; 0.001, and p \u0026lt; 0.001 for the trend). This result was consistent with the classification by WHO (Model 3: OR = 0.88, 95% CI: 0.82-0.94, p \u0026lt; 0.001). Next, we analyzed CaCO₃ concentration as a continuous variable. The results indicated that higher CaCO₃ levels were associated with a lower prevalence of UC (Model 3: OR = 0.93, 95% CI: 0.90-0.96, p \u0026lt; 0.001), with consistent findings observed for Ca\u0026sup2;⁺ concentration (Model 3: OR = 0.93, 95% CI: 0.90-0.96, p \u0026lt; 0.001). As for prevalent CD, significant protective effects of very hard water were found in Model 1 (OR = 0.87, 95% CI: 0.78-0.97, p = 0.011, and p = 0.016 for the trend) and Model 3 (OR = 0.88, 95% CI: 0.79-0.99, p = 0.027, and p = 0.039 for the trend). When classified according to the WHO classification, the effect was only observed in Model 1 (OR = 0.90, 95% CI: 0.82-0.99, p = 0.029). Results remained significant when analyzed continuous Ca\u0026sup2;⁺ concentration in all three models and CaCO₃ concentration in Model 1 and Model 3. When analyzing the overall prevalence of IBD, the protective effect of hard water was consistent with the results observed in the separate analyses for UC and CD (Supplementary Table S1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBaseline characteristics of participants in the cohort study.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn the cohort study, a total of 475,895 participants were included, among whom 3,212 participants were diagnosed with IBD (1,035 CD and 2,166 UC) during the mean follow-up of 14.56 years. The mean age was 56.56 years for non-IBD participants and 57.27 years for those with IBD. A slightly higher proportion of male participants were diagnosed with IBD (50.1%). Detailed characteristics were showed in Table 3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eIncreased water hardness was significantly associated with a decreased risk of CD but not UC.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn the cohort study, hard water (120-180 mg/l) and very hard water (\u0026gt;180 mg/l), as classified by USGS, were found to be significantly associated with a reduced risk of incident CD in all three models (see Table 4 for details, Model 3: HR = 0.84, 95% CI: 0.73-0.97, p = 0.016, and p = 0.007 for the trend). When analyzing CaCO₃ concentration as a continuous variable, each SD increase in concentration was also significantly associated with a reduced incidence of CD in three models (Model 3: HR = 0.93, 95% CI: 0.87-0.99, p = 0.017). However, when analyzed according to the WHO classification, the results were not significant (see Table 4). Similarly, analyzing Ca\u0026sup2;⁺ concentration as a continuous variable did not show a significant association (see Table 4). While analyzing the overall incidence of IBD, very hard water classified by the USGS (Model 3: HR =0.92, 95% CI: 0.84-1.00, p = 0.040, and p = 0.025 for the trend), hard water classified by WHO (HR = 0.92, 95% CI: 0.85-0.99, p = 0.021), and continuous CaCO₃ concentration (HR = 0.96, 95% CI: 0.92-0.99, p = 0.014) all showed significant protective effects (Supplementary Table S2). However, when UC was analyzed separately, these associations were no longer significant (see Table 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eThe protective effect of hard water is more significant for individuals with low genetic risk for CD.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe further evaluated the protective effect of hard water on the incident CD stratified by genetic risk. The results revealed more significant protective effects of hard water (HR = 0.35, 95% CI: 0.17-0.70, p = 0.003) and very hard water (HR = 0.74, 95% CI: 0.57-0.95, p = 0.019), as categorized by the USGS, among individuals with a low genetic risk for CD compared with the high genetic group (see Table 5). Nonetheless, the protective effect of hard water was also validated in the high genetic risk group (HR = 0.66, 95% CI: 0.45-0.97, p = 0.035). When analyzing CaCO₃ concentration within subgroups, a significant association was observed only among low genetic risk group for CD (HR = 0.88, 95% CI: 0.79-0.99, p = 0.032). The combined analysis of water hardness and CD genetic risk showed no significant interaction in reducing CD incidence (all p-interaction \u0026gt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eSubgroup and sensitivity analyses\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn the subgroup analysis, the association between water hardness and the risk of CD and UC was further examined, stratifying by factors such as age, CCI scores, BMI, IPAQ physical activity levels, alcohol consumption, smoking status, ethnicity, TDI, and diet quality scores (Supplementary Table S3-S12) Overall, stronger protective effects of water hardness on risk of CD were observed in the low-to-moderate IPAQ physical activity group, the group with alcohol consumption below weekly frequency, and among smokers. Although hard water showed no effect on the overall risk of UC, subgroup analysis revealed a protective effect among male, individuals with low-to-moderate physical activity, and non-smokers.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn sensitivity analyses, we obtained consistent results when using multiple imputation to handle covariates, excluding participants diagnosed within the first year of follow-up, and excluding participants with both UC and CD diagnoses. Additionally, similar findings were observed when further adjusting for C-reactive protein, residential area, waist circumference, and educational level as covariates. Results remained comparable when using self-reported sex instead of genetic sex. (Supplementary Table S13-S20)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this large-scale population-based cross-sectional and cohort study consisting of 481,468 participants in the UK Biobank, our findings indicate that hard water is associated with a reduced prevalence of IBD. Additionally, we report the association between hard water and a decreased incidence of CD in participants without IBD at baseline. However, water hardness did not influence UC incidence. Consistently, an increase in CaCO₃ concentration was associated with a reduction in IBD prevalence and CD incidence, whereas no association was found between magnesium concentrations and IBD. The protective effect on CD risk is more pronounced among individuals with low genetic susceptibility. Besides, results also varied across different physical activity, alcohol consumption and smoking status subgroups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough previous research has shown that calcium intake may have protective benefits for IBD, the relationship between water hardness and IBD remains unexplored.[11, 21] A previous case-controlled study showed that higher dietary calcium intake was correlated with a reduced prevalence of UC.[21] Another cohort study revealed that participants consuming milk have significantly lower risk of developing CD.[11] However, the underlying mechanisms have not been fully understood. Calcium is the most prevalent cation in the human body and acts as a ubiquitous second messenger, influencing various cellular functions such as differentiation, apoptosis, and proliferation.[22] Calcium are also closely related to barrier permeability and immune response.[23] The regulatory role of calcium ions at the cellular level in IBD has been well-documented, and dietary calcium intake has also been shown to alleviate colitis in mouse models via the TNF-\u0026alpha; pathway.[24] In the meanwhile, calcium supplementation could modulate gut microbiota, which might be a potential mechanism underlying its beneficial effects on IBD.[25] While previous research has suggested that magnesium may alleviate colitis and improve intestinal barrier function,[26] our study did not find significant associations between water magnesium concentrations and the prevalence or incidence of IBD.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWater is a fundamental necessity for life. The associations between water quality and health-related outcomes carry significant public health implications.[27] Earlier research has examined the impact of water hardness on different health conditions.[9, 10, 28] A large-scale study examining water hardness and both all-cause and cause-specific cancers found that hard water has a protective effect against several types of cancer, including gastrointestinal cancers such as esophageal, stomach, and colorectal cancers.[10] Another study based on the UK Biobank revealed the association between water hardness and eczema.[9] Several studies have focused on the relationship between water quality and IBD, which evaluated several metal ions and other quality index.[12, 13] A study on UK tap water suggested that the effects of water composition on health may be mediated through modulation of the gut microbiota.[29] However, evidence on the association between water hardness and IBD risk remains limited. This study is the first to identify a protective effect of hard water on both the prevalence and incidence of IBD.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough no significant interaction effect between water hardness and IBD was found, the protective effect of hard water on the risk of CD was significantly stronger in participants with lower genetic susceptibility to CD. The pathological processes of IBD are triggered by both genetic and environmental factors.[30, 31] Previous studies have identified numerous potential loci and their interactions with environmental factors.[30] Mode of diet and nutrition intake potentially interact with susceptible gene loci, regulating the course of IBD through mechanisms such as gut microbiota and immune responses.[31] Researchers also found that the impact of dietary iron intake on IBD was significantly modified by a coding variant in Fc\u0026gamma;RIIA gene, providing evidence for an environmental metal-gene interaction in the progression of IBD.[32] However, the potential interaction effect between calcium and IBD susceptible gene variants remains unclear and warrants further investigation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere are several strengths of our study. Firstly, our study is a population-based cross-sectional and cohort study with large sample size and long-term follow-up. The combination of cross-sectional and longitudinal analyses provides more comprehensive evidence to support the conclusions. Secondly, to our knowledge, this is the first study to evaluate the associations between water hardness and the prevalence and incidence of IBD. We adjusted potential confounding variables such as genetic risk, alcohol consumption and smoking status and provided robust statistical evidence. Thirdly, we have considered the influence of genetic factors on IBD risk. The interaction effect between genetics and water hardness were further analyzed. We examined how water quality impacts groups with varying levels of genetic risk differently, providing evidence for the combined influence of environmental and genetic factors in the pathogenesis of IBD. \u0026nbsp; However, there are still limitations of our study. Firstly, the data we obtained from the UK Biobank pertains to the water supply of the area where participants reside. One limitation is that the actual water source of some participants may not be tap water. However, due to data availability constraints, we were unable to obtain this part of information. Secondly, other water quality data are not available in UK Biobank, such as pH, metal concentrations, which limits our further evaluations. Thirdly, because the participants in this study were primarily of White British descent, the generalizability of the conclusions to other ethnic groups is unclear. Fourthly, the participants in this study were aged 40-69, which may not fully reflect the population of individuals with an early onset of disease.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study reveals the protective effects of water quality on IBD and highlights its differential impact across groups with varying genetic risk. Hard water is associated with lower prevalence of UC and CD, and reduces the risk of incident CD as well. This effect is more pronounced among participants with lower genetic risk of CD. Our findings provide valuable implications for public health strategies and disease prevention, offering important insights into the potential role of environmental factors, such as water quality, in modulating IBD risk. This highlights the importance of considering environmental factors alongside genetic susceptibility when developing preventive measures and strategies for managing IBD. Further research is needed to confirm these associations and explore the underlying mechanisms linking water quality, genetic risk, and IBD.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBMI, Body mass index\u003c/p\u003e\n\u003cp\u003eCCI, Charlson Comorbidity Index\u003c/p\u003e\n\u003cp\u003eCD, Crohn\u0026rsquo;s disease\u003c/p\u003e\n\u003cp\u003eGWAS, Genome-wide association study\u003c/p\u003e\n\u003cp\u003eHR, Hazard ratios\u003c/p\u003e\n\u003cp\u003eIBD, Inflammatory bowel diseases\u003c/p\u003e\n\u003cp\u003eICD, International Classification of Diseases\u003c/p\u003e\n\u003cp\u003eIPAQ, International Physical Activity Questionnaire\u003c/p\u003e\n\u003cp\u003eOR, Odds ratios\u003c/p\u003e\n\u003cp\u003ePRS, Polygenic risk scores\u003c/p\u003e\n\u003cp\u003eTDI,\u0026nbsp;Townsend Deprivation Index\u003c/p\u003e\n\u003cp\u003eUC, Ulcerative colitis\u003c/p\u003e\n\u003cp\u003eUSGS, United States Geological Survey\u003c/p\u003e\n\u003cp\u003eWHO, World Health Organization\u003c/p\u003e\n\u003cp\u003e95% CI, 95% Confidence intervals\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe UK Biobank received ethical approval from the North West-Haydock Research Ethics Committee (REC reference: 16/NW/0274). Informed consent was obtained from all participants at the time of recruitment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data analyzed during this study are included in this article and its supplementary information files.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by High-Level Talent Science and Technology Innovation Leading Talent Program of Zhejiang Province, reference number: 2023R5239.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKexin Ye: data processing, data analysis, table editing, original draft writing. Tianyu Zhou, Zhenhe Jin: methodology, data processing, manuscript editing. Wenxi Jiang, Zhaoxue Liu: methodology, manuscript editing. Linwen Luo, Yize Wang: table editing, manuscript editing. Zhe Shen: supervision, funding acquisition, conceptualization, project administration.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted under the application number of 176969 of UK Biobank. We sincerely acknowledge the contributions of the participants and the UK Biobank team.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZhao M, G\u0026ouml;nczi L, Lakatos PL, Burisch J. The Burden of Inflammatory Bowel Disease in Europe in 2020. J Crohns Colitis. 2021;15:1573\u0026ndash;87.\u003c/li\u003e\n\u003cli\u003eAdolph TE, Meyer M, Schw\u0026auml;rzler J, Mayr L, Grabherr F, Tilg H. The metabolic nature of inflammatory bowel diseases. Nat Rev Gastroenterol Hepatol. 2022;19:753\u0026ndash;67.\u003c/li\u003e\n\u003cli\u003eAgrawal M, Allin KH, Petralia F, Colombel J-F, Jess T. Multiomics to elucidate inflammatory bowel disease risk factors and pathways. Nat Rev Gastroenterol Hepatol. 2022;19:399\u0026ndash;409.\u003c/li\u003e\n\u003cli\u003eVedamurthy A, Ananthakrishnan AN. Influence of Environmental Factors in the Development and Outcomes of Inflammatory Bowel Disease. Gastroenterol Hepatol. 2019;15:72.\u003c/li\u003e\n\u003cli\u003eJairath V, Feagan BG. Global burden of inflammatory bowel disease. Lancet Gastroenterol Hepatol. 2020;5:2\u0026ndash;3.\u003c/li\u003e\n\u003cli\u003eZhao M, Feng R, Ben-Horin S, Zhuang X, Tian Z, Li X, et al. Systematic review with meta-analysis: environmental and dietary differences of inflammatory bowel disease in Eastern and Western populations. Aliment Pharmacol Ther. 2022;55:266\u0026ndash;76.\u003c/li\u003e\n\u003cli\u003eCaruso R, Lo BC, N\u0026uacute;\u0026ntilde;ez G. Host\u0026ndash;microbiota interactions in inflammatory bowel disease. Nat Rev Immunol. 2020;20:411\u0026ndash;26.\u003c/li\u003e\n\u003cli\u003eYang AZ, Jostins-Dean L. Environmental variables and genome-environment interactions predicting IBD diagnosis in large UK cohort. Sci Rep. 2022;12:10890.\u003c/li\u003e\n\u003cli\u003eLopez DJ, Singh A, Waidyatillake NT, Su JC, Bui DS, Dharmage SC, et al. The association between domestic hard water and eczema in adults from the UK Biobank cohort study. Br J Dermatol. 2022;187:704\u0026ndash;12.\u003c/li\u003e\n\u003cli\u003eYang H, Wang Q, Zhang S, Zhang J, Zhang Y, Feng J. Association of Domestic Water Hardness with All-Cause and Cause-Specific Cancers: Evidence from 447,996 UK Biobank Participants. Environ Health Perspect. 2024;132:067008.\u003c/li\u003e\n\u003cli\u003eOpstelten JL, Leenders M, Dik VK, Chan SSM, van Schaik FDM, Khaw K-T, et al. Dairy Products, Dietary Calcium, and Risk of Inflammatory Bowel Disease: Results From a European Prospective Cohort Investigation. Inflamm Bowel Dis. 2016;22:1403\u0026ndash;11.\u003c/li\u003e\n\u003cli\u003eAamodt G, Bukholm G, Jahnsen J, Moum B, Vatn MH, the IBSEN Study Group. The Association Between Water Supply and Inflammatory Bowel Disease Based on a 1990\u0026ndash;1993 Cohort Study in Southeastern Norway. Am J Epidemiol. 2008;168:1065\u0026ndash;72.\u003c/li\u003e\n\u003cli\u003eBagherzadeh F, Karami Horestani M, Sadeghi M, Ahmadi A, Bahreini R, Fadaei A, et al. Influence of metal ions concentration in drinking water in the development of ulcerative colitis. Int J Environ Sci Technol. 2022;19:3539\u0026ndash;46.\u003c/li\u003e\n\u003cli\u003eSudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12:e1001779.\u003c/li\u003e\n\u003cli\u003eCraig CL, Marshall AL, Sj\u0026ouml;str\u0026ouml;m M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35:1381\u0026ndash;95.\u003c/li\u003e\n\u003cli\u003eGuillaume E, Pornet C, Dejardin O, Launay L, Lillini R, Vercelli M, et al. Development of a cross-cultural deprivation index in five European countries. J Epidemiol Community Health. 2015;70:493.\u003c/li\u003e\n\u003cli\u003eSundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol. 2004;57:1288\u0026ndash;94.\u003c/li\u003e\n\u003cli\u003eZhuang P, Liu X, Li Y, Wan X, Wu Y, Wu F, et al. Effect of Diet Quality and Genetic Predisposition on Hemoglobin A1c and Type 2 Diabetes Risk: Gene-Diet Interaction Analysis of 357,419 Individuals. Diabetes Care. 2021;44:2470\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eSw C, Ts M, Pf O. Tutorial: a guide to performing polygenic risk score analyses. Nat Protoc. 2020;15.\u003c/li\u003e\n\u003cli\u003eBuuren S van, Groothuis-Oudshoorn K. mice: Multivariate Imputation by Chained Equations in R. J Stat Softw. 2011;45:1\u0026ndash;67.\u003c/li\u003e\n\u003cli\u003eHajhashemy Z, Saneei P, Keshteli AH, Daghaghzadeh H, Tavakkoli H, Adibi P, et al. A population based case\u0026ndash;control study of association between dietary calcium intake and ulcerative colitis in adults. Sci Rep. 2022;12:7913.\u003c/li\u003e\n\u003cli\u003eBerridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol. 2000;1:11\u0026ndash;21.\u003c/li\u003e\n\u003cli\u003eDalal PJ, Muller WA, Sullivan DP. Endothelial Cell Calcium Signaling during Barrier Function and Inflammation. Am J Pathol. 2020;190:535\u0026ndash;42.\u003c/li\u003e\n\u003cli\u003eZhu Y, Mahon BD, Froicu M, Cantorna MT. Calcium and 1\u0026alpha;,25‐dihydroxyvitamin D3 target the TNF‐\u0026alpha; pathway to suppress experimental inflammatory bowel disease. https://doi.org/10.1002/eji.200425491.\u003c/li\u003e\n\u003cli\u003eChaplin A, Parra P, Laraichi S, Serra F, Palou A. Calcium supplementation modulates gut microbiota in a prebiotic manner in dietary obese mice. Mol Nutr Food Res. 2016;60:468\u0026ndash;80.\u003c/li\u003e\n\u003cli\u003eTrapani V, Petito V, Di Agostini A, Arduini D, Hamersma W, Pietropaolo G, et al. Dietary Magnesium Alleviates Experimental Murine Colitis Through Upregulation of the Transient Receptor Potential Melastatin 6 Channel. Inflamm Bowel Dis. 2018;24:2198\u0026ndash;210.\u003c/li\u003e\n\u003cli\u003eLi P, Wu J. Drinking Water Quality and Public Health. Expo Health. 2019;11:73\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eJabbar‐Lopez ZK, Craven J, Logan K, Greenblatt D, Marrs T, Radulovic S, et al. Longitudinal analysis of the effect of water hardness on atopic eczema: evidence for gene\u0026ndash;environment interaction. Br J Dermatol. 2020;183:285\u0026ndash;93.\u003c/li\u003e\n\u003cli\u003eBowyer RCE, Schillereff DN, Jackson MA, Le Roy C, Wells PM, Spector TD, et al. Associations between UK tap water and gut microbiota composition suggest the gut microbiome as a potential mediator of health differences linked to water quality. Sci Total Environ. 2020;739:139697.\u003c/li\u003e\n\u003cli\u003eGraham DB, Xavier RJ. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature. 2020;578:527\u0026ndash;39.\u003c/li\u003e\n\u003cli\u003eNoble AJ, Nowak JK, Adams AT, Uhlig HH, Satsangi J. Defining Interactions Between the Genome, Epigenome, and the Environment in Inflammatory Bowel Disease: Progress and Prospects. Gastroenterology. 2023;165:44-60.e2.\u003c/li\u003e\n\u003cli\u003eKhalili H, de Silva PS, Ananthakrishnan AN, Lochhead P, Joshi A, Garber JJ, et al. Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohn\u0026rsquo;s Disease and Ulcerative Colitis. Inflamm Bowel Dis. 2017;23:1088\u0026ndash;95.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Characteristics of participants according to IBD status and subtype in the cross-sectional study\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"56%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-IBD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIBD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=475895)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=5573)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=1803)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=3750)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e56.57\u0026nbsp;(8.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e57.31\u0026nbsp;(7.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e56.69\u0026nbsp;(8.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e57.61\u0026nbsp;(7.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGenetic sex, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e258383 (54.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2903 (52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e998\u0026nbsp;(55.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1895\u0026nbsp;(50.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e217512 (45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2670 (47.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e805\u0026nbsp;(44.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1855\u0026nbsp;(49.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEthnicity, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e448558 (94.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e5334 (95.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1725\u0026nbsp;(95.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e3589\u0026nbsp;(95.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e26849 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e233 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e76\u0026nbsp;(4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e157\u0026nbsp;(4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e488 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e6 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation levels, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eCollege or university\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e154180 (32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1557 (27.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e467\u0026nbsp;(25.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1086\u0026nbsp;(29)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e321223 (67.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4010 (72.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1334\u0026nbsp;(74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2660\u0026nbsp;(70.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e492 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e6 (0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTownsend deprivation index, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e-1.3\u0026nbsp;(3.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e-1.26\u0026nbsp;(3.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e-1.08\u0026nbsp;(3.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e-1.35\u0026nbsp;(3.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e27.44\u0026nbsp;(4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e27.15\u0026nbsp;(4.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e26.84\u0026nbsp;(4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e27.3\u0026nbsp;(4.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiet Score, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e49.57\u0026nbsp;(14.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e46.82\u0026nbsp;(15.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e44.76\u0026nbsp;(15.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e47.82\u0026nbsp;(15.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharlson Comorbidity Index, mean (SD)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.22 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.36 (0.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.38\u0026nbsp;(0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.38\u0026nbsp;(0.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIPAQ activity, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e150314\u0026nbsp;(31.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1629\u0026nbsp;(29.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e503\u0026nbsp;(27.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1120\u0026nbsp;(29.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e149592\u0026nbsp;(31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1674\u0026nbsp;(30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e519\u0026nbsp;(28.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1151\u0026nbsp;(30.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e68027\u0026nbsp;(14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e907\u0026nbsp;(16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e319\u0026nbsp;(17.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e586\u0026nbsp;(15.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e107962\u0026nbsp;(22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1363\u0026nbsp;(24.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e462\u0026nbsp;(25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e893\u0026nbsp;(23.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlcohol, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eDaily or almost daily\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e96867\u0026nbsp;(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1028\u0026nbsp;(18.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e285\u0026nbsp;(15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e741\u0026nbsp;(19.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eThree or four times a week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e109971\u0026nbsp;(23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1185\u0026nbsp;(21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e356\u0026nbsp;(19.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e820\u0026nbsp;(21.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eOne to four times a week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e122608\u0026nbsp;(25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1389\u0026nbsp;(24.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e449\u0026nbsp;(24.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e939\u0026nbsp;(25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eOne to three times a month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e52814\u0026nbsp;(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e663\u0026nbsp;(11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e234\u0026nbsp;(13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e427\u0026nbsp;(11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eNever or special occasions only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e92590\u0026nbsp;(19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1297\u0026nbsp;(23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e476\u0026nbsp;(26.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e815\u0026nbsp;(21.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1045\u0026nbsp;(0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e11\u0026nbsp;(0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e3\u0026nbsp;(0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e8\u0026nbsp;(0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eEver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e282980\u0026nbsp;(59.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e3584\u0026nbsp;(64.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1186\u0026nbsp;(65.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2385\u0026nbsp;(63.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eNever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e190538\u0026nbsp;(40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1967\u0026nbsp;(35.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e610\u0026nbsp;(33.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1350\u0026nbsp;(36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eNot know\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2377\u0026nbsp;(0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e22\u0026nbsp;(0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e7\u0026nbsp;(0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e15\u0026nbsp;(0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater hardness (USGS), n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e0-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e169376\u0026nbsp;(35.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2163\u0026nbsp;(38.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e695\u0026nbsp;(38.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1459\u0026nbsp;(38.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e60-120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e94420\u0026nbsp;(19.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1115\u0026nbsp;(20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e347\u0026nbsp;(19.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e762\u0026nbsp;(20.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e120-180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e28236\u0026nbsp;(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e342\u0026nbsp;(6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e107\u0026nbsp;(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e232\u0026nbsp;(6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026gt;180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e183530\u0026nbsp;(38.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1951\u0026nbsp;(35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e654\u0026nbsp;(36.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1295\u0026nbsp;(34.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater hardness (WHO), n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026lt;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e294657\u0026nbsp;(62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e3655\u0026nbsp;(65.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1163\u0026nbsp;(64.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2474\u0026nbsp;(66)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026ge;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e180905\u0026nbsp;(38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1916\u0026nbsp;(34.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e640\u0026nbsp;(35.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1274\u0026nbsp;(34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCaCO\u003csub\u003e3\u003c/sub\u003e concentration, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e146.19\u0026nbsp;(114.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e136.69\u0026nbsp;(112.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e137.64\u0026nbsp;(113.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e135.7\u0026nbsp;(111.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCa concentration, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e51.3\u0026nbsp;(40.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e48.28\u0026nbsp;(39.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e47.99\u0026nbsp;(39.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e48.45\u0026nbsp;(39.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMg concentration, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4.6\u0026nbsp;(3.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4.57\u0026nbsp;(3.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4.55\u0026nbsp;(3.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4.57\u0026nbsp;(3.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: BMI, Body mass index; IPAQ, International Physical Activity Questionnaire; USGS, United States Geological Survey; WHO, World Health Organization.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Association between water hardness and prevalent UC and CD in the cross-sectional study\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"97%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater hardness (USGS, mg/l)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e0-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e695\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e1459\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e60-120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n 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\u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.95\u0026nbsp;(0.77-1.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.620\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e232\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.96\u0026nbsp;(0.84-1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.583\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.97\u0026nbsp;(0.85-1.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.694\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.98\u0026nbsp;(0.85-1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.797\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026gt;180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e654\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.87\u0026nbsp;(0.78-0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.90\u0026nbsp;(0.81-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.88\u0026nbsp;(0.79-0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.027\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e1295\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.83\u0026nbsp;(0.77-0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.84\u0026nbsp;(0.78-0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.86\u0026nbsp;(0.80-0.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003eP for trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.039\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater hardness (WHO, mg/l)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026lt;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e1163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e2474\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026ge;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.90\u0026nbsp;(0.82-0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.029\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.92\u0026nbsp;(0.83-1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.90\u0026nbsp;(0.82-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e1274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.85\u0026nbsp;(0.79-0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.86\u0026nbsp;(0.80-0.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.88\u0026nbsp;(0.82-0.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCaCO\u003csub\u003e3\u003c/sub\u003e concentration (per SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.94\u0026nbsp;(0.89-0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.95\u0026nbsp;(0.91-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.041\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.94\u0026nbsp;(0.90-0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.92\u0026nbsp;(0.89-0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.92\u0026nbsp;(0.89-0.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.93\u0026nbsp;(0.90-0.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCa concentration (per SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.92\u0026nbsp;(0.88-0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.93\u0026nbsp;(0.89-0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.93\u0026nbsp;(0.88-0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.93\u0026nbsp;(0.90-0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.94\u0026nbsp;(0.91-0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.95\u0026nbsp;(0.92-0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMg concentration (per SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.99 (0.95-1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.814\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e1.00\u0026nbsp;(0.95-1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.985\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e1.00\u0026nbsp;(0.95-1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.918\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.99\u0026nbsp;(0.96-1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.99\u0026nbsp;(0.96-1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.626\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.00\u0026nbsp;(0.96-1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.895\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAbbreviations: USGS, United States Geological Survey; WHO, World Health Organization.\u003c/p\u003e\n\u003cp\u003eModel 1: adjusted for age and sex; Model 2: adjusted for age, sex, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI and diet quality scores; Model 3: adjusted for age, sex, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI, diet quality scores, the first five principal components of ancestry genetics and PRS scores.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Characteristics of participants according to IBD status and subtype in the cohort study\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"56%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-IBD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIBD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=472683)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=3212)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=1035)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e(n=2166)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e56.56\u0026nbsp;(8.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e57.27\u0026nbsp;(8.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e56.97\u0026nbsp;(8.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e57.42\u0026nbsp;(7.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGenetic sex, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e256779\u0026nbsp;(54.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1598\u0026nbsp;(49.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e561\u0026nbsp;(54.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1037\u0026nbsp;(47.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e215904\u0026nbsp;(45.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1603\u0026nbsp;(50.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e474\u0026nbsp;(45.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1129\u0026nbsp;(52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEthnicity, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eWhite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e445543\u0026nbsp;(94.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e3005\u0026nbsp;(93.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e976\u0026nbsp;(94.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2029\u0026nbsp;(93.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e26656\u0026nbsp;(5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e192\u0026nbsp;(6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e58\u0026nbsp;(5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e134\u0026nbsp;(6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e484\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e3\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation levels, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eCollege or university\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e153372\u0026nbsp;(32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e807\u0026nbsp;(25.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e266\u0026nbsp;(25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e541\u0026nbsp;(25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e318823\u0026nbsp;(67.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2390\u0026nbsp;(74.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e768\u0026nbsp;(74.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1622\u0026nbsp;(74.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e488\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e3\u0026nbsp;(0.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTownsend deprivation index, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e-1.31\u0026nbsp;(3.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e-0.89\u0026nbsp;(3.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e-0.71\u0026nbsp;(3.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e-0.97\u0026nbsp;(3.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e27.43\u0026nbsp;(4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e27.98\u0026nbsp;(5.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e28.08\u0026nbsp;(5.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e27.93\u0026nbsp;(4.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiet Score, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e49.59\u0026nbsp;(14.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e47.89\u0026nbsp;(15.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e47.18\u0026nbsp;(15.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e48.22\u0026nbsp;(15.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharlson Comorbidity Index, mean (SD)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.22\u0026nbsp;(0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.33\u0026nbsp;(0.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.33\u0026nbsp;(0.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e0.34\u0026nbsp;(0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIPAQ activity, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e149363\u0026nbsp;(31.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e947\u0026nbsp;(29.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e287\u0026nbsp;(27.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e660\u0026nbsp;(30.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e148657\u0026nbsp;(31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e931\u0026nbsp;(29.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e320\u0026nbsp;(30.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e611\u0026nbsp;(28.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e67547\u0026nbsp;(14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e479\u0026nbsp;(15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e156\u0026nbsp;(15.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e323\u0026nbsp;(14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e107116\u0026nbsp;(22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e844\u0026nbsp;(26.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e272\u0026nbsp;(26.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e572\u0026nbsp;(26.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlcohol, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eDaily or almost daily\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e96205\u0026nbsp;(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e661\u0026nbsp;(20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e200\u0026nbsp;(19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e461\u0026nbsp;(21.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eThree or four times a week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e109344\u0026nbsp;(23.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e625\u0026nbsp;(19.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e195\u0026nbsp;(18.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e430\u0026nbsp;(19.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eOne to four times a week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e121809\u0026nbsp;(25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e794\u0026nbsp;(24.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e242\u0026nbsp;(23.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e552\u0026nbsp;(25.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eOne to three times a month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e52468\u0026nbsp;(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e346\u0026nbsp;(10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e120\u0026nbsp;(11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e226\u0026nbsp;(10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eNever or special occasions only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e91821\u0026nbsp;(19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e766\u0026nbsp;(23.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e276\u0026nbsp;(26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e490\u0026nbsp;(22.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1036\u0026nbsp;(0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e9\u0026nbsp;(0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2\u0026nbsp;(0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e7\u0026nbsp;(0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eEver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e280777\u0026nbsp;(59.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2194\u0026nbsp;(68.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e705\u0026nbsp;(68.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1489\u0026nbsp;(68.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eNever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e189545\u0026nbsp;(40.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e991\u0026nbsp;(31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e328\u0026nbsp;(31.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e663\u0026nbsp;(30.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2361\u0026nbsp;(0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e16\u0026nbsp;(0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2\u0026nbsp;(0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e14\u0026nbsp;(0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater hardness (USGS), n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e0-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e168183\u0026nbsp;(35.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1191\u0026nbsp;(37.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e415\u0026nbsp;(40.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e776\u0026nbsp;(35.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e60-120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e93755\u0026nbsp;(19.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e661\u0026nbsp;(20.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e206\u0026nbsp;(19.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e455\u0026nbsp;(21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e120-180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e28052\u0026nbsp;(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e183\u0026nbsp;(5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e37\u0026nbsp;(3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e146\u0026nbsp;(6.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026gt;180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e182363\u0026nbsp;(38.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1163\u0026nbsp;(36.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e375\u0026nbsp;(36.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e788\u0026nbsp;(36.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater hardness (WHO), n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026lt;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e292598\u0026nbsp;(61.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e2052\u0026nbsp;(64.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e664\u0026nbsp;(64.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1388\u0026nbsp;(64.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026ge;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e179755\u0026nbsp;(38.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e1146\u0026nbsp;(35.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e369\u0026nbsp;(35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e777\u0026nbsp;(35.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCaCO\u003csub\u003e3\u003c/sub\u003e concentration, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e145.68\u0026nbsp;(115.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e139.8\u0026nbsp;(112.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e137\u0026nbsp;(113.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e141.09\u0026nbsp;(112.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCa concentration, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e51.1\u0026nbsp;(40.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e51.02\u0026nbsp;(40.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e49.33\u0026nbsp;(40.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e51.79\u0026nbsp;(40.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMg concentration, mean (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4.58\u0026nbsp;(3.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4.46\u0026nbsp;(3.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4.35\u0026nbsp;(3.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4.51\u0026nbsp;(3.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: BMI, Body mass index; IPAQ, International Physical Activity Questionnaire; USGS, United States Geological Survey; WHO, World Health Organization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Association between water hardness and incident UC and CD in the cohort study\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"97%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModel 3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater hardness (USGS, mg/l)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e0-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e415\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e776\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e60-120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.89\u0026nbsp;(0.75-1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.91\u0026nbsp;(0.77-1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.90\u0026nbsp;(0.76-1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e455\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.05\u0026nbsp;(0.93-1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.06\u0026nbsp;(0.94-1.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.07\u0026nbsp;(0.95-1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.260\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e120-180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.53\u0026nbsp;(0.38-0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.56\u0026nbsp;(0.40-0.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.55\u0026nbsp;(0.39-0.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.13\u0026nbsp;(0.95-1.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.15\u0026nbsp;(0.97-1.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.16\u0026nbsp;(0.97-1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.094\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026gt;180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e375\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.84\u0026nbsp;(0.73-0.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.85\u0026nbsp;(0.74-0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.024\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.84\u0026nbsp;(0.73-0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.016\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.95\u0026nbsp;(0.86-1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.275\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.95\u0026nbsp;(0.85-1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.96\u0026nbsp;(0.87-1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003eP for trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.258\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.262\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.452\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater hardness (WHO, mg/l)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026lt;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e664\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e1388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u0026ge;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e369\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.91\u0026nbsp;(0.8-1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.91\u0026nbsp;(0.8-1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.167\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.90\u0026nbsp;(0.79-1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e777\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.92\u0026nbsp;(0.84-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.92\u0026nbsp;(0.84-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.054\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.93\u0026nbsp;(0.85-1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.106\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCaCO\u003csub\u003e3\u003c/sub\u003e concentration (per SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.93\u0026nbsp;(0.87-0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.020\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.93\u0026nbsp;(0.87-0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.027\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.93\u0026nbsp;(0.87-0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.97\u0026nbsp;(0.93-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.97\u0026nbsp;(0.93-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.97\u0026nbsp;(0.93-1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.223\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCa concentration (per SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.96\u0026nbsp;(0.9-1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.95\u0026nbsp;(0.89-1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.95\u0026nbsp;(0.89-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.03\u0026nbsp;(0.98-1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.02\u0026nbsp;(0.98-1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.310\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.03\u0026nbsp;(0.98-1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMg concentration (per SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.93\u0026nbsp;(0.87-1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.95\u0026nbsp;(0.88-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 7px;\"\u003e\n \u003cp\u003e0.94\u0026nbsp;(0.88-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.98\u0026nbsp;(0.94-1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.473\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e0.99\u0026nbsp;(0.95-1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.693\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e1.00\u0026nbsp;(0.95-1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e0.848\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAbbreviations: USGS, United States Geological Survey; WHO, World Health Organization.\u003c/p\u003e\n\u003cp\u003eModel 1: adjusted for age and sex; Model 2: adjusted for age, sex, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI and diet quality scores; Model 3: adjusted for age, sex, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI, diet quality scores, the first five principal components of ancestry genetics and PRS scores.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5. Association between water hardness and the risk of CD by genetic susceptibility\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"58%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLow genetic risk\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHigh genetic risk\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP for interaction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHR (95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater hardness (USGS, mg/l)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e60-120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.87\u0026nbsp;(0.65-1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.342\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.92\u0026nbsp;(0.75-1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.211\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e120-180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.35\u0026nbsp;(0.17-0.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.66\u0026nbsp;(0.45-0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.035\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026gt;180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.794\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.74\u0026nbsp;(0.57-0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.019\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.89\u0026nbsp;(0.75-1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.457\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eP for trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.008\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.162\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWater hardness (WHO, mg/l)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026lt;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003eref\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026ge;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.427\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.83\u0026nbsp;(0.66-1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.94\u0026nbsp;(0.80-1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.446\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCaCO\u003csub\u003e3\u003c/sub\u003e concentration (per SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.348\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.88\u0026nbsp;(0.79-0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.032\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.95\u0026nbsp;(0.88-1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.171\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCa concentration (per SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.90\u0026nbsp;(0.80-1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.97\u0026nbsp;(0.90-1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMg concentration (per SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17px;\"\u003e\n \u003cp\u003e0.655\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.02 (0.81-1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0.95\u0026nbsp;(0.88-1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e0.285\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: USGS, United States Geological Survey; WHO, World Health Organization.\u003c/p\u003e\n\u003cp\u003eAdjusted for age, sex, CCI scores, BMI, IPAQ physical activity, alcohol consumption, smoking status, ethnicity, TDI, diet quality scores, the first five principal components of ancestry genetics.\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Inflammatory bowel disease, water hardness, cohort study, cross-sectional study","lastPublishedDoi":"10.21203/rs.3.rs-5552821/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5552821/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEnvironmental factors play a significant role in the pathogenesis of inflammatory bowel disease. This study aims to investigate the association between water hardness and both the prevalence and incidence of Crohn’s disease and ulcerative colitis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCross-sectional study and cohort study were respectively conducted based on 481,468 participants in the UK Biobank. Multivariate logistics regression and Cox proportional hazards regression were used to evaluate the association between water hardness and Crohn’s disease and ulcerative colitis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 481,468 participants were included in the cross-sectional study. Increased water hardness was correlated with reduced prevalence of Crohn’s disease (OR = 0.88, 95% CI: 0.79-0.99, p = 0.027, and p = 0.039 for the trend) and ulcerative colitis (OR = 0.83, 95% CI: 0.77-0.89, p \u0026lt; 0.001, and p \u0026lt; 0.001 for the trend). A total of 475,895 participants with the mean follow-up of 14.6 years were included in the cohort study. During the follow-up period, 1033 developed Crohn’s disease and 2165 developed ulcerative colitis. Increased water hardness was significantly associated with a decreased risk of Crohn’s disease (HR = 0.84, 95% CI: 0.73-0.97, p = 0.016, and p = 0.007 for the trend) but not ulcerative colitis. We also found that the protective effect of very hard water is more significant for individuals with low genetic risk for Crohn’s disease (HR = 0.74, 95% CI: 0.57-0.95, p = 0.019).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHigher water hardness is associated with a decreased prevalence of both Crohn’s disease and ulcerative colitis, as well as a reduced incidence of Crohn’s disease. However, no significant association was observed with the incidence of ulcerative colitis.\u003c/p\u003e","manuscriptTitle":"The Protective Effect of Hard Water on Ulcerative Colitis and Crohn's Disease: A Cross-Sectional and Cohort Study of 481,468 Participants in the UK Biobank","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-12 05:02:18","doi":"10.21203/rs.3.rs-5552821/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"03afba26-3ce3-480d-911b-ca77cf10766f","owner":[],"postedDate":"March 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-21T04:38:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-12 05:02:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5552821","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5552821","identity":"rs-5552821","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}