Alcohol consumption and the risk of rheumatoid arthritis

Abstract Background Though accumulated evidence has indicated an inverse relationship between alcohol intake and rheumatoid arthritis (RA) risk, it remained uncertain whether such association was causal or biased by confounding. We aimed to explore the dose-response relationship and the potential causality between alcohol consumption and RA risk by using both prospective study and Mendelian randomization (MR). Methods We first performed an updated meta-analysis on the association between alcohol consumption and the RA risk in PubMed and Web of Science database. Then we assessed the association of alcohol intake-related phenotypes with RA risk based on UK Biobank. The association was examined using Cox regression, while the potential non-linear relationship was modeled by restricted cubic splines (RCS). Stratification analyses based on sex, age, and ethnicity, as well as a series of sensitivity analyses were further performed. In addition, linkage disequilibrium score regression (LDSC) was used to calculate the heritability and genetic correlation between these traits, and two-sample MR was employed to assess the association of genetically predicted alcohol consumption with the risk of RA. Results Findings from the meta-analysis suggested an inverse association between alcohol intake and RA (relative risk (RR): 0.85; 95% confidence interval (CI): 0.78, 0.83). Similarly, in UK Biobank cohort, one standard deviation increases of alcohol intake per day was related to a 6% lower risk of RA (hazard ratio (HR): 0.94; 95% CI: 0.91, 0.97). RCS models revealed a J-shaped dose-response association between alcohol consumption and RA, with moderate intake associated with a reduced risk. However, alcohol use disorder (AUD) was associated with a 30% higher risk of RA (HR: 1.30; 95% CI: 1.08, 1.56). A sex- and age-dependent association of alcohol intake and RA was observed in stratification analysis. Findings from LDSC and MR both suggested AUD as a potential risk factor for RA, while no statistically significant association between alcohol consumption and RA was observed. Conclusion Our study revealed a dose- and sex- dependent pattern of alcohol consumption on RA risk. Though a slightly protective effect was observed during a specific range of alcohol consumption, it should not be recommended as a prevention strategy for RA.