{"paper_id":"2b0c6802-1aaa-42e3-a822-dcfeff995db9","body_text":"A Mendelian randomization study on the causal effects of dietary components on arterial stiffness | 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 A Mendelian randomization study on the causal effects of dietary components on arterial stiffness Jingming Yao, Canwei Chen, Shiqu Deng, Ming Yang, Wenhui Xie This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5819129/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 Arterial stiffness (AS) is a prevalent issue affecting the elderly population, emerges as a significant risk factor for cardiovascular events (CVs), yet the impact of dietary components remains inconclusive. Methods This study employs a two-sample Mendelian randomization (MR) framework to assess the causal association between specific nutrients and AS risk. Genomewide association study (GWAS) summary statistics for wheat products, pork, mutton, sugar as exposures, with the AS index as the outcome. Results Utilizing the inverse variance weighted (IVW) method, genetically informed MR analysis reveals a noteworthy inverse correlation between wheat product consumption and AS risk (IVW, β: -2.043, 95% confidence interval(CI): [-2.724; -1.364], P = 3.87×10 9 ). Conversely, there exists a positive correlation between the intake of pork and mutton and the risk of AS. No significant links are observed for sugar consumption. Conclusions Increased wheat product intake reduces AS risk, while heightened pork and mutton intake elevates it, offering critical insights for AS prevention. arterial stiffness dietary components genome-wide association study two-sample Mendelian randomization Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Population aging is a global phenomenon, with China anticipated to have the largest population of older adults [ 1 ]. Aging, linked to a decline in homeostatic regulation efficiency, correlates with increasing morbidity and mortality from cardiovascular events (CVs) [ 2 ]. Arterial stiffness (AS) emerges as a pivotal CV risk factor, traditionally assessed through carotidfemoral pulse wave velocity (PWV), AS is a prevalent issue affecting the elderly population. Alternatively, noninvasive infrared finger sensors (photoplethysmography) offer a convenient method for recording digital blood volume waveforms, yielding the arterial stiffness index (ASI) in seconds [ 3 ]. ASI is particularly well suited for large cohort population studies due to its quick acquisition, aligning closely with other assessment methods like PWV and the augmentation index [ 4 ]. Notably, a community based population study revealed a significant association between higher ASI with increased risk of various cardiovascular diseases (CVDs), including myocardial infarction, coronary heart disease, heart failure, and allcause mortality [ 5 ]. While existing research has explored the AS-CV relationship[ 6 – 8 ], further investigation is needed to understand the factors influencing AS for improved cardiovascular disease prevention and treatment. Healthy eating, characterized by balanced macronutrient intake, adequate micronutrients, and hydration [ 9 ], has consistently demonstrated an inverse relationship with CV risks [ 10 ]. The impact of individual dietary components on cardiovascular health is crucial, with the Mediterranean diet, for instance, showcasing benefits in reducing blood pressure and AS [ 11 ]. Conflicting findings exist regarding the association of sugar with AS, with some studies linking sugar, including fructose, to elevated PWV [ 12 , 13 ] while others report no such connection [ 14 ]. Similarly, the role of dairy fat consumption in CV risk is nuanced [ 15 ]; some studies suggest a favorable impact on reducing AS [ 16 ]. Wheat product intake is also similarly associated with lower CV risk [ 17 , 18 ]. These varying effects underscore the need for a comprehensive examination of dietary components and their inconsistent associations with AS in population based studies [ 19 ]. Mendelian randomization (MR), a powerful epidemiological tool utilizing genetic variants such as singlenucleotide polymorphisms (SNPs), offers advantages in terms of time, financial efficiency, and resource use compared to traditional clinical trials [ 20 ]. MR analysis has several advantages over traditional clinical trials in terms of time, as well as financial and material resources. It has been used widely in various fields of study [ 21 ]. Leveraging MR, this study utilizes largescale genomewide association study (GWAS) data to assess the potential causal effects of diverse dietary components on AS, providing valuable insights for CVD prevention. Materials and Methods Study design and assumption MR analysis, which leverages genetic instrumental variables (Ivs) to examine the causal nexus between an exposure and an outcome, is predicated on three tenets: (1) The IVs are clearly associated with the exposure, (2) the IVs are independent of any confounders of the exposure-outcome association, and (3) the IVs have observable impacts on the outcome variable that are exclusively conferred via the exposure variable. Single nucleotide polymorphisms (SNPs) are IVs that occur randomly throughout a population and can be used as reliable indicators of lifelong effects. Single SNPs have been widely used as biological markers for MR analyses. This process is illustrated in Fig. 1 . Data source We retrieved genetic association data for both the exposure and the outcome from an independent GWAS with non-overlapping samples, to investigate the effects of various dietary components on AS. Exposure and Outcome All summary statistics based on association data were available free of charge. The GWAS summary statistics for the dietary components were downloaded from the IEU Open GWAS Project ( https://gwas.mrcieu.ac.uk/ ). The exposures were the intakes of wheat products (dataset: ukb-b-3599, Sample size: 461,046); lamb/mutton (dataset: ukb-b-14179, Sample size: 460,006); sugar or foods/drinks containing sugar (dataset: ukb-b-5495, Sample size: 461,046)); Outcome data were based on the ASI (ebi-a-GCST008403, Sample size: 127,121). Selection of IVs for MR analyses Appropriate IVs for the MR analyses were rigorously obtained from the GWAS summary results. First, a stringent threshold of genome-wide significance (P < 5×10 − 8) was applied to select the SNPs. A P-value of < 5×10 − 6 was considered sufficient for SNPs concerning exposures to dairy products. Second, to ensure genetic independence and avoid pleiotropy, only SNPs with linkage disequilibrium values of R2 > 0.01 in the European 1000 Genome reference panel and no significant associations with the outcome (P < 5×10 − 8) were retained. Statistical analysis The F-statistic was used to assess the strength of the exposure, and values of F < 10 indicated weak instrument strength. We used the MR-Egger intercept test to detect the presence of horizontal pleiotropy [ 22 ]. Randomeffects inverse-variance weighted (IVW), weighted median, and weighted mode methods were used as statistical approaches to estimate the potential causality between dietary components and AS. IVW, our primary analysis method, is based on the assumption that all of the core principles of MR are satisfied. The findings of our MR analysis are presented in Table 1. P-values of < 0.05 were taken to reflect causality between dietary components and AS. All statistical analyses were conducted using R version 4.3.1 (TUNA Team, Tsinghua University,China) with the “TwoSample MR” package (version 0.5.7). Results Effect of wheat products on ASI Five independent SNPs associated with wheat products were selected as IVs to estimate the effects of wheat products on ASI. The F-statistic of these IVs was 43.88. Genetically predicted wheat products were inversely associated with highrisk ASI using the IVW method (β: -2.044, 95% confidence interval[CI]: (-2.724; -1.364), P = 3.87×10^-9). The weighted median method(β: -2.173, 95%CI: (-2.989; -1.357), P = 1.79-9) and weighted mode (β: -1.428, 95%CI: (-2.302; -0.554), P = 0.032) showed con-sistent results. No significant heterogeneity was observed according to MR-PRESSO scores ( P = 0.362). No significant horizontal pleiotropy was observed according to the MR-Egger regression intercept test (intercept=–0.00932, P = 0.31). The effective values of the individual IVs of wheat products on ASI were visualized on a scatterplot (Fig. 2 ) Effects of Pork products on ASI We estimated the causal impact of pork on ASI, We observed a positive correlation between genetically predicted pork intake and the risk of ASI using an IVW approach(β: 0.306, 95%CI: (0.077; 0.536), P = 0.009; Fig. 3 ), with an F-statistic for these IVs of 266.93. However, the impact of pork intake on ASI did not reach statistical significance for the other three MR methods(MR-Egger, Weighted median and Weighted mode), Our MR-PRESSO analysis revealed that the heterogeneity of pork was not significant ( P = 0.623). Moreover, an MR-Egger regression intercept test did not provide significant evidence of horizontal pleiotropy. Effects of Mutton products on ASI Mutton intake also had a positive correlation with highrisk ASI when using the IVW approach (β: 0.235, 95%CI: (0.082; 0.388), P = 0.003; Fig. 4 ).The F-statistic for these IVs was 626.44..For mutton intake, only the weighted median approach showed a statistical significance ( P = 0.02), whereas there was no statistical difference found using the other two methods(MR-Egger and Weighted mode). The sensitivity analyses showed that the Mutton associated with AS were not heterogeneous (P = 0.343, Q-test) or horizontally pleiotropic (P > 0.05, MR-Egger’s intercept method) Effect of sugar on ASI Sugar, a ubiquitous component of food, not only imparts a sweet taste but also serves as a preservative and humectant. It is regularly added to a range of processed foods, including soft drinks, cakes, cookies, breakfast cereals, and other snacks. In this study, we used four MR methods to investigate the effects of sugar intake on ASI. The effect of sugar on ASI, as predicted by genetic variants, did not reach statistical significance using any of the MR methods (Table 1). Heterogeneity was not significant according to our MR-PRESSO analysis ( P = 0.83), and there was no significant evidence of horizontal pleiotropy according to an MR-Egger regression intercept test (intercept = 0.0049, P = 0.383). Discussion In this study, we observed a negative correlation between wheat products and highrisk ASI. Conversely, pork and mutton were positively correlated with high-risk ASI. However, we did not find any significant impact of sugar on ASI. As has been mentioned previously, wheat products have been found to significantly reduce CVs in some studies [ 18 ]; however, the mechanism behind this is not fully understood. AS is a significant risk factor for CVs. Genetically predicted wheat products were found to be inversely associated with the risk of AS in this MR study. Our results suggested that reducing AS in wheat products may represent a key strategy for reducing the occurrence of CVs. Further research is warranted to confirm these findings. Other studies have also demonstrated a close correlation between red meat consumption and CVs [ 23 , 24 ] owing to high levels of cholesterol of red meat, saturated fatty acids, and sodium. There was a positive causal relationship identified between genetically predicted pork and mutton intake and AS in this MR study. Traditional epidemiological studies may also help provide preliminary insights into the correlation between red meat and AS. MR studies have the advantage of yielding more precise and dependable results when examining the correlation between red meat intake and AS. Recent studies have suggested a higher risk of CVs in individuals with high normal glucose levels [ 25 , 26 ], indicating a potential link between blood glucose levels and cardiovascular health. It has been well established that AS is an independent risk factor for adverse CVs and allcause mortality in the general population [ 27 ], and also serves as an independent predictor of mortality in diabetes mellitus (DM) [ 28 ]. Additionally, higher blood glucose levels are associated with a higher degree of AS in patients with type 2 DM (T2DM) [ 29 , 30 ]. Interestingly, added sugar intake was not associated with AS in type 1 DM (T1DM)with higher body mass index (BMI) z-scores but was positively correlated with PWV trunk measurements in patients with T1DM who had lower BMI z-scores [ 31 ]. The inconsistencies present in the results of these studies may be related to the impact of sugar intake on AS, which varies between different populations. However, in this study, sugar intake was not associated with AS as determined by all four MR methods, suggesting that sugar intake did not represent a significant risk factor for AS in our sample. Our findings, supported by genetic variants, lend credence to the theory that sugar consumption does not contribute to CVs by affecting AS. Nevertheless, other mechanisms may also contribute to the relationship between sugar intake and cardiovascular health. This study had several notable strengths. Samples of both the exposure and outcome datasets were derived from a large GWAS cohort, and multiple sensitivity analyses were conducted to reduce the false-positive rates. However, it also had several key limitations as well. First, despite the use of MR analysis, the correlation between genetically predicted red meat intake and high-risk ASI was statistically significant only when using the IVW approach. Second, our Cochran's Q test failed to completely eliminate all heterogeneity. Moreover, the restriction of our population to those of European descent may limit the generalizability of our findings to other ethnicities. Several reports have discussed the relationship between dietary components and AS [19,35], but have failed to produce consistent results. To our knowledge, there have been no reports thus far on the effect of dietary components on AS that have used MR analyses. Our findings offer a fresh perspective for a comprehensive understanding of the dietary factors that influence AS, and are expected to offer new ideas and strategies for the prevention and management of AS through dietary interventions. Conclusions Our findings suggest that increased wheat product intake reduces the risk of AS, while increased red meat intake increases it. Sugar may not affect AS. This study provides new insights into the prevention of AS from a dietary perspective. Declarations Ethics approval and consent to participate: Not applicable. Consent for publication : Not applicable. Availability of data and Materials: Summary data are available online at www.ukbiobank.ac.uk/data-showcase and Open GWAS Project (https://gwas.mrcieu.ac.uk/). Acknowledgments: We would like to express our gratitude to ieu open gwas project (https://gwas.mrcieu.ac.uk/datasets/) for providing summary results data for these analyses. Funding: This work was supported by National Natural Science Foundation of China (82301772), the Fujian Natural Science Foundation (2023J01655), the Investigator Initiation Fund Project of Fujian Medical University Union Hospital (2022XH047), and the Startup Fund for Scientific Research from Fujian Medical University (2022QH1026), Quanzhou Municipa Science and Technology Plan Project (Grant Number: 2022NS019) Conflict of Interest: The authors declare no conflict of interest. Author contributions: Writing—original draft preparation:Jingming Yao and Canwei Chen; Writing—review and editing, Canwei Chen and Shiqu Deng; Formal analysis—Canwei Chen, Jingming Yao;Supervision, Wenhui Xie; Project administration, Ming Yang and Wenhui Xie. All authors have read and agreed to the published version of the manuscript. References Jiang Q, Feng Q. Editorial: Aging and health in China. Front Public Health. 2022;10:998769. https:doi:10.3389/fpubh.2022.998769 . Fajemiroye JO, da Cunha LC, Saavedra-Rodríguez R, Rodrigues KL, Naves LM, Mourão AA, da Silva EF, Williams NEE, Martins JLR, Sousa RB, Rebelo ACS, Reis A, Santos RDS, Ferreira-Neto ML, Pedrino GR. Aging-Induced Biological Changes and Cardiovascular Diseases. Biomed Res Int. 2018; 2018:7156435.https:doi:10.1155/2018/7156435 . Millasseau SC, Guigui FG, Kelly RP, Prasad K, Cockcroft JR, Ritter JM, Chowienczyk PJ. Noninvasive assessment of the digital volume pulse. Comparison with the peripheral pressure pulse. 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Dietary patterns are associated with arterial stiffness and carotid atherosclerosis in postmenopausal women. Endocrine. 2022;78(1):57–67.https:doi: 10.1007/s12020-022-03152-2 . Tables Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.xlsx 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-5819129\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":403251528,\"identity\":\"25190ef4-14c2-4837-a1f8-62a5195c1f0b\",\"order_by\":0,\"name\":\"Jingming Yao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Minhou County Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jingming\",\"middleName\":\"\",\"lastName\":\"Yao\",\"suffix\":\"\"},{\"id\":403251529,\"identity\":\"71c26a60-a034-45e9-9318-d43a284e383e\",\"order_by\":1,\"name\":\"Canwei Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Nan'an Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Canwei\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":403251530,\"identity\":\"7ec2e4f6-969c-4370-ae5d-41ec44b2f7d3\",\"order_by\":2,\"name\":\"Shiqu Deng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center), Fujian Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shiqu\",\"middleName\":\"\",\"lastName\":\"Deng\",\"suffix\":\"\"},{\"id\":403251531,\"identity\":\"beb94693-2316-47ec-8a28-430a5f4dfeee\",\"order_by\":3,\"name\":\"Ming Yang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Fujian Medical University, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fujian Medical University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Ming\",\"middleName\":\"\",\"lastName\":\"Yang\",\"suffix\":\"\"},{\"id\":403251532,\"identity\":\"fe01a3fc-bfb1-4af1-9a0c-bc5d98efe2e2\",\"order_by\":4,\"name\":\"Wenhui Xie\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABD0lEQVRIiWNgGAWjYDCCAxCKB0QwMzBIyLE3HICycWthbEDWYsxzgEgtDDBliT0H4GzsgO948/MHH/ccluGXSD72uLDNIr2H8XSaBEOFdWID+9kD2LRInjlm2DjjWRqP5Iy0dOOZbRK5PQxnt0kwnElPbODJS8CmxeBGDmMzzwEbHoPbOWbSvEAt+0FaGNsOJzZI8Bjg0SLBY387/xtISzoPWMs/glqAtkjnsIG0JEC0NODWAvLLzBkH0ngk7j8zk+Y5J2EI9Mtmi4Rj6cZtPDlYtQBD7MGHDwcO2/P3HH4mzVNWJ88jcXbjjQ811rL97GewasECJA4wMCQAaTYi1QMBfwPxakfBKBgFo2BEAACcimBUlE3WlwAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"Fujian Medical University, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fujian Medical University\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Wenhui\",\"middleName\":\"\",\"lastName\":\"Xie\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-01-13 10:38:20\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-5819129/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-5819129/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":74286585,\"identity\":\"46955cc2-e4a0-4be1-9d00-5f32569451d3\",\"added_by\":\"auto\",\"created_at\":\"2025-01-20 16:15:56\",\"extension\":\"jpg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":100002,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eFlowchart of the study.\\u003c/p\\u003e\\n\\u003cp\\u003eGWAS, genome wide association study; SNPs, single nucleotide polymorphisms; MR, Mendelian randomization.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Fig.1.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5819129/v1/bb9837d9570f41df750d5db9.jpg\"},{\"id\":74286646,\"identity\":\"f4088249-531b-409c-854e-c5b5ea154e1d\",\"added_by\":\"auto\",\"created_at\":\"2025-01-20 16:16:01\",\"extension\":\"jpg\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":627700,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e[A] Scatter plot of our MR analyses regarding the association between wheat products and AS.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Fig.2.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5819129/v1/1aa0e146a5901f3f33db5ef0.jpg\"},{\"id\":74286614,\"identity\":\"d442bc3f-51bc-4feb-ba26-a5cb0ec6854a\",\"added_by\":\"auto\",\"created_at\":\"2025-01-20 16:15:58\",\"extension\":\"jpg\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":651564,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eScatterplot of our MR analyses regarding the association between pork intake and AS.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Fig.3.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5819129/v1/adc0936efdf15745a0b8c89f.jpg\"},{\"id\":74286586,\"identity\":\"64c43a93-05a2-4956-ab08-1c70fc8b6210\",\"added_by\":\"auto\",\"created_at\":\"2025-01-20 16:15:56\",\"extension\":\"jpg\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":546550,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eScatterplot of our MR analysis for lamb/mutton intake and AS.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Fib.4.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5819129/v1/273260665a5f9eaf944c561a.jpg\"},{\"id\":74288607,\"identity\":\"66bea7b6-ea8d-41d1-99e7-860b77c9f43b\",\"added_by\":\"auto\",\"created_at\":\"2025-01-20 16:24:07\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":2485561,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5819129/v1/22aa89c6-1a91-4914-abf7-fde1c716aff4.pdf\"},{\"id\":74286620,\"identity\":\"4ea956a8-d3b2-4317-9e28-21eaad3b1c99\",\"added_by\":\"auto\",\"created_at\":\"2025-01-20 16:16:00\",\"extension\":\"xlsx\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":11569,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Table1.xlsx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5819129/v1/cd33ed559c7e9501c86690f8.xlsx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"A Mendelian randomization study on the causal effects of dietary components on arterial stiffness\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003ePopulation aging is a global phenomenon, with China anticipated to have the largest population of older adults [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. Aging, linked to a decline in homeostatic regulation efficiency, correlates with increasing morbidity and mortality from cardiovascular events (CVs) [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e]. Arterial stiffness (AS) emerges as a pivotal CV risk factor, traditionally assessed through carotidfemoral pulse wave velocity (PWV), AS is a prevalent issue affecting the elderly population. Alternatively, noninvasive infrared finger sensors (photoplethysmography) offer a convenient method for recording digital blood volume waveforms, yielding the arterial stiffness index (ASI) in seconds [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. ASI is particularly well suited for large cohort population studies due to its quick acquisition, aligning closely with other assessment methods like PWV and the augmentation index [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. Notably, a community based population study revealed a significant association between higher ASI with increased risk of various cardiovascular diseases (CVDs), including myocardial infarction, coronary heart disease, heart failure, and allcause mortality [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. While existing research has explored the AS-CV relationship[\\u003cspan additionalcitationids=\\\"CR7\\\" citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e], further investigation is needed to understand the factors influencing AS for improved cardiovascular disease prevention and treatment.\\u003c/p\\u003e \\u003cp\\u003eHealthy eating, characterized by balanced macronutrient intake, adequate micronutrients, and hydration [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e], has consistently demonstrated an inverse relationship with CV risks [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]. The impact of individual dietary components on cardiovascular health is crucial, with the Mediterranean diet, for instance, showcasing benefits in reducing blood pressure and AS [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. Conflicting findings exist regarding the association of sugar with AS, with some studies linking sugar, including fructose, to elevated PWV [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e] while others report no such connection [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. Similarly, the role of dairy fat consumption in CV risk is nuanced [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]; some studies suggest a favorable impact on reducing AS [\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. Wheat product intake is also similarly associated with lower CV risk [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]. These varying effects underscore the need for a comprehensive examination of dietary components and their inconsistent associations with AS in population based studies [\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eMendelian randomization (MR), a powerful epidemiological tool utilizing genetic variants such as singlenucleotide polymorphisms (SNPs), offers advantages in terms of time, financial efficiency, and resource use compared to traditional clinical trials [\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e]. MR analysis has several advantages over traditional clinical trials in terms of time, as well as financial and material resources. It has been used widely in various fields of study [\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. Leveraging MR, this study utilizes largescale genomewide association study (GWAS) data to assess the potential causal effects of diverse dietary components on AS, providing valuable insights for CVD prevention.\\u003c/p\\u003e\"},{\"header\":\"Materials and Methods\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy design and assumption\\u003c/h2\\u003e \\u003cp\\u003eMR analysis, which leverages genetic instrumental variables (Ivs) to examine the causal nexus between an exposure and an outcome, is predicated on three tenets: (1) The IVs are clearly associated with the exposure, (2) the IVs are independent of any confounders of the exposure-outcome association, and (3) the IVs have observable impacts on the outcome variable that are exclusively conferred via the exposure variable. Single nucleotide polymorphisms (SNPs) are IVs that occur randomly throughout a population and can be used as reliable indicators of lifelong effects. Single SNPs have been widely used as biological markers for MR analyses. This process is illustrated in Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eData source\\u003c/h3\\u003e\\n\\u003cp\\u003eWe retrieved genetic association data for both the exposure and the outcome from an independent GWAS with non-overlapping samples, to investigate the effects of various dietary components on AS.\\u003c/p\\u003e\\n\\u003ch3\\u003eExposure and Outcome\\u003c/h3\\u003e\\n\\u003cp\\u003eAll summary statistics based on association data were available free of charge. The GWAS summary statistics for the dietary components were downloaded from the IEU Open GWAS Project (\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://gwas.mrcieu.ac.uk/\\u003c/span\\u003e\\u003cspan address=\\\"https://gwas.mrcieu.ac.uk/\\\" targettype=\\\"URL\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e). The exposures were the intakes of wheat products (dataset: ukb-b-3599, Sample size: 461,046); lamb/mutton (dataset: ukb-b-14179, Sample size: 460,006); sugar or foods/drinks containing sugar (dataset: ukb-b-5495, Sample size: 461,046)); Outcome data were based on the ASI (ebi-a-GCST008403, Sample size: 127,121).\\u003c/p\\u003e\\n\\u003ch3\\u003eSelection of IVs for MR analyses\\u003c/h3\\u003e\\n\\u003cp\\u003eAppropriate IVs for the MR analyses were rigorously obtained from the GWAS summary results. First, a stringent threshold of genome-wide significance (P\\u0026thinsp;\\u0026lt;\\u0026thinsp;5\\u0026times;10\\u0026thinsp;\\u0026minus;\\u0026thinsp;8) was applied to select the SNPs. A P-value of \\u0026lt;\\u0026thinsp;5\\u0026times;10\\u0026thinsp;\\u0026minus;\\u0026thinsp;6 was considered sufficient for SNPs concerning exposures to dairy products. Second, to ensure genetic independence and avoid pleiotropy, only SNPs with linkage disequilibrium values of R2\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.01 in the European 1000 Genome reference panel and no significant associations with the outcome (P\\u0026thinsp;\\u0026lt;\\u0026thinsp;5\\u0026times;10\\u0026thinsp;\\u0026minus;\\u0026thinsp;8) were retained.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec7\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical analysis\\u003c/h2\\u003e \\u003cp\\u003eThe F-statistic was used to assess the strength of the exposure, and values of F\\u0026thinsp;\\u0026lt;\\u0026thinsp;10 indicated weak instrument strength. We used the MR-Egger intercept test to detect the presence of horizontal pleiotropy [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. Randomeffects inverse-variance weighted (IVW), weighted median, and weighted mode methods were used as statistical approaches to estimate the potential causality between dietary components and AS. IVW, our primary analysis method, is based on the assumption that all of the core principles of MR are satisfied. The findings of our MR analysis are presented in Table\\u0026nbsp;1. P-values of \\u0026lt;\\u0026thinsp;0.05 were taken to reflect causality between dietary components and AS. All statistical analyses were conducted using R version 4.3.1 (TUNA Team, Tsinghua University,China) with the \\u0026ldquo;TwoSample MR\\u0026rdquo; package (version 0.5.7).\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cdiv id=\\\"Sec9\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eEffect of wheat products on ASI\\u003c/h2\\u003e \\u003cp\\u003eFive independent SNPs associated with wheat products were selected as IVs to estimate the effects of wheat products on ASI. The F-statistic of these IVs was 43.88. Genetically predicted wheat products were inversely associated with highrisk ASI using the IVW method (β: -2.044, 95% confidence interval[CI]: (-2.724; -1.364), \\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;3.87\\u0026times;10^-9). The weighted median method(β: -2.173, 95%CI: (-2.989; -1.357), \\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;1.79-9) and weighted mode (β: -1.428, 95%CI: (-2.302; -0.554), \\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;0.032) showed con-sistent results. No significant heterogeneity was observed according to MR-PRESSO scores (\\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;0.362). No significant horizontal pleiotropy was observed according to the MR-Egger regression intercept test (intercept=\\u0026ndash;0.00932, \\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;0.31). The effective values of the individual IVs of wheat products on ASI were visualized on a scatterplot (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e)\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\\n\\u003ch3\\u003eEffects of Pork products on ASI\\u003c/h3\\u003e\\n\\u003cp\\u003eWe estimated the causal impact of pork on ASI, We observed a positive correlation between genetically predicted pork intake and the risk of ASI using an IVW approach(β: 0.306, 95%CI: (0.077; 0.536), \\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;0.009; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e), with an F-statistic for these IVs of 266.93. However, the impact of pork intake on ASI did not reach statistical significance for the other three MR methods(MR-Egger, Weighted median and Weighted mode), Our MR-PRESSO analysis revealed that the heterogeneity of pork was not significant (\\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;0.623). Moreover, an MR-Egger regression intercept test did not provide significant evidence of horizontal pleiotropy.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cdiv id=\\\"Sec11\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eEffects of Mutton products on ASI\\u003c/h2\\u003e \\u003cp\\u003eMutton intake also had a positive correlation with highrisk ASI when using the IVW approach (β: 0.235, 95%CI: (0.082; 0.388), \\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;0.003; Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e).The F-statistic for these IVs was 626.44..For mutton intake, only the weighted median approach showed a statistical significance (\\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;0.02), whereas there was no statistical difference found using the other two methods(MR-Egger and Weighted mode). The sensitivity analyses showed that the Mutton associated with AS were not heterogeneous (P\\u0026thinsp;=\\u0026thinsp;0.343, Q-test) or horizontally pleiotropic (P\\u0026thinsp;\\u0026gt;\\u0026thinsp;0.05, MR-Egger\\u0026rsquo;s intercept method)\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec12\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eEffect of sugar on ASI\\u003c/h2\\u003e \\u003cp\\u003eSugar, a ubiquitous component of food, not only imparts a sweet taste but also serves as a preservative and humectant. It is regularly added to a range of processed foods, including soft drinks, cakes, cookies, breakfast cereals, and other snacks. In this study, we used four MR methods to investigate the effects of sugar intake on ASI. The effect of sugar on ASI, as predicted by genetic variants, did not reach statistical significance using any of the MR methods (Table\\u0026nbsp;1). Heterogeneity was not significant according to our MR-PRESSO analysis (\\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;0.83), and there was no significant evidence of horizontal pleiotropy according to an MR-Egger regression intercept test (intercept\\u0026thinsp;=\\u0026thinsp;0.0049, \\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;0.383).\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eIn this study, we observed a negative correlation between wheat products and highrisk ASI. Conversely, pork and mutton were positively correlated with high-risk ASI. However, we did not find any significant impact of sugar on ASI.\\u003c/p\\u003e \\u003cp\\u003eAs has been mentioned previously, wheat products have been found to significantly reduce CVs in some studies [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]; however, the mechanism behind this is not fully understood. AS is a significant risk factor for CVs. Genetically predicted wheat products were found to be inversely associated with the risk of AS in this MR study. Our results suggested that reducing AS in wheat products may represent a key strategy for reducing the occurrence of CVs. Further research is warranted to confirm these findings.\\u003c/p\\u003e \\u003cp\\u003eOther studies have also demonstrated a close correlation between red meat consumption and CVs [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e] owing to high levels of cholesterol of red meat, saturated fatty acids, and sodium. There was a positive causal relationship identified between genetically predicted pork and mutton intake and AS in this MR study. Traditional epidemiological studies may also help provide preliminary insights into the correlation between red meat and AS. MR studies have the advantage of yielding more precise and dependable results when examining the correlation between red meat intake and AS.\\u003c/p\\u003e \\u003cp\\u003eRecent studies have suggested a higher risk of CVs in individuals with high normal glucose levels [\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e], indicating a potential link between blood glucose levels and cardiovascular health. It has been well established that AS is an independent risk factor for adverse CVs and allcause mortality in the general population [\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e], and also serves as an independent predictor of mortality in diabetes mellitus (DM) [\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e]. Additionally, higher blood glucose levels are associated with a higher degree of AS in patients with type 2 DM (T2DM) [\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e]. Interestingly, added sugar intake was not associated with AS in type 1 DM (T1DM)with higher body mass index (BMI) z-scores but was positively correlated with PWV trunk measurements in patients with T1DM who had lower BMI z-scores [\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e]. The inconsistencies present in the results of these studies may be related to the impact of sugar intake on AS, which varies between different populations. However, in this study, sugar intake was not associated with AS as determined by all four MR methods, suggesting that sugar intake did not represent a significant risk factor for AS in our sample. Our findings, supported by genetic variants, lend credence to the theory that sugar consumption does not contribute to CVs by affecting AS. Nevertheless, other mechanisms may also contribute to the relationship between sugar intake and cardiovascular health.\\u003c/p\\u003e \\u003cp\\u003eThis study had several notable strengths. Samples of both the exposure and outcome datasets were derived from a large GWAS cohort, and multiple sensitivity analyses were conducted to reduce the false-positive rates. However, it also had several key limitations as well. First, despite the use of MR analysis, the correlation between genetically predicted red meat intake and high-risk ASI was statistically significant only when using the IVW approach. Second, our Cochran's Q test failed to completely eliminate all heterogeneity. Moreover, the restriction of our population to those of European descent may limit the generalizability of our findings to other ethnicities.\\u003c/p\\u003e \\u003cp\\u003eSeveral reports have discussed the relationship between dietary components and AS [19,35], but have failed to produce consistent results. To our knowledge, there have been no reports thus far on the effect of dietary components on AS that have used MR analyses. Our findings offer a fresh perspective for a comprehensive understanding of the dietary factors that influence AS, and are expected to offer new ideas and strategies for the prevention and management of AS through dietary interventions.\\u003c/p\\u003e\"},{\"header\":\"Conclusions\",\"content\":\"\\u003cp\\u003eOur findings suggest that increased wheat product intake reduces the risk of AS, while increased red meat intake increases it. Sugar may not affect AS. This study provides new insights into the prevention of AS from a dietary perspective.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate:\\u0026nbsp;\\u003c/strong\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e: Not applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and Materials:\\u0026nbsp;\\u003c/strong\\u003eSummary data are available online at www.ukbiobank.ac.uk/data-showcase and Open GWAS Project (https://gwas.mrcieu.ac.uk/).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgments:\\u0026nbsp;\\u003c/strong\\u003eWe would like to express our gratitude to ieu open gwas project (https://gwas.mrcieu.ac.uk/datasets/) for providing summary results data for these analyses.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding:\\u003c/strong\\u003e This work was supported by National Natural Science Foundation of China (82301772), the Fujian Natural Science Foundation (2023J01655), the Investigator Initiation Fund Project of Fujian Medical University Union Hospital (2022XH047), and the Startup Fund for Scientific Research from Fujian Medical University (2022QH1026), Quanzhou Municipa Science and Technology Plan Project (Grant Number: 2022NS019)\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflict of Interest:\\u003c/strong\\u003e The authors declare no conflict of interest.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor contributions:\\u0026nbsp;\\u003c/strong\\u003eWriting\\u0026mdash;original draft preparation:Jingming Yao and Canwei Chen; Writing\\u0026mdash;review and editing, Canwei Chen and Shiqu Deng; Formal analysis\\u0026mdash;Canwei Chen, Jingming Yao;Supervision, Wenhui Xie; Project administration, Ming Yang and Wenhui Xie. 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Endocrine. 2022;78(1):57\\u0026ndash;67.https:doi:\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1007/s12020-022-03152-2\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s12020-022-03152-2\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003eTable 1 is available in the Supplementary Files section.\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"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\":\"info@researchsquare.com\",\"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\":\"arterial stiffness, dietary components, genome-wide association study, two-sample Mendelian randomization\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-5819129/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-5819129/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground\\u003c/h2\\u003e \\u003cp\\u003eArterial stiffness (AS) is a prevalent issue affecting the elderly population, emerges as a significant risk factor for cardiovascular events (CVs), yet the impact of dietary components remains inconclusive.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e \\u003cp\\u003eThis study employs a two-sample Mendelian randomization (MR) framework to assess the causal association between specific nutrients and AS risk. Genomewide association study (GWAS) summary statistics for wheat products, pork, mutton, sugar as exposures, with the AS index as the outcome.\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e \\u003cp\\u003eUtilizing the inverse variance weighted (IVW) method, genetically informed MR analysis reveals a noteworthy inverse correlation between wheat product consumption and AS risk (IVW, β: -2.043, 95% confidence interval(CI): [-2.724; -1.364], \\u003cem\\u003eP\\u0026thinsp;=\\u003c/em\\u003e\\u0026thinsp;3.87\\u0026times;10\\u003csup\\u003e9\\u003c/sup\\u003e). Conversely, there exists a positive correlation between the intake of pork and mutton and the risk of AS. No significant links are observed for sugar consumption.\\u003c/p\\u003e\\u003ch2\\u003eConclusions\\u003c/h2\\u003e \\u003cp\\u003eIncreased wheat product intake reduces AS risk, while heightened pork and mutton intake elevates it, offering critical insights for AS prevention.\\u003c/p\\u003e\",\"manuscriptTitle\":\"A Mendelian randomization study on the causal effects of dietary components on arterial stiffness\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-01-20 16:15:11\",\"doi\":\"10.21203/rs.3.rs-5819129/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"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\":\"1759d5e8-e86f-45fa-8f8e-81a502bd5cb3\",\"owner\":[],\"postedDate\":\"January 20th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-01-20T16:15:50+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-01-20 16:15:11\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-5819129\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-5819129\",\"identity\":\"rs-5819129\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}