Abstract
BACKGROUND: Rheumatoid arthritis (RA) is a complex multifactorial autoimmune disease affected by genetics and environmental factors. The relationship between alcohol consumption and RA remains controversial. This study aimed to assess the association between alcohol consumption and RA risk using cross-sectional analysis and Mendelian randomization (MR). METHODS: We investigated the association between alcohol consumption and RA risk through multivariate linear regression and subgroup analyses. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 which involved 32,308 participants. Subsequently, a two-sample MR study was conducted to assess the causal effect of spirits intake on RA. Instrumental variables (IVs) for spirits intake were screened from genome-wide association study (GWAS) datasets, including 69,949 individuals from the UK Biobank study, while summary statistics relating to RA were obtained from a GWAS meta-analysis of 417,256 participants. The primary inverse variance weighted (IVW) method and other supplementary MR methods were used to estimate the causal association between spirits intake and RA. Sensitivity analyses were performed to confirm the robustness and reliability of the results. RESULTS: In the cross-sectional analysis, we observed that alcohol consumption was significantly positively linked with RA risk (odds ratio [OR] = 1.030; 95% confidence interval [CI], 1.025-1.034). According to subgroup analyses stratified by age, sex, race, smoking status, marital status, education attainment, and body mass index (BMI), consistently showed a positive relationship between alcohol consumption and RA risk in each subgroup (all OR > 1, P < 0.05). Furthermore, MR analysis indicated a causal association between spirits intake and RA (OR = 1.043, P < 0.05). Sensitivity analyses supported the robustness and reliability of these findings (all P > 0.05). CONCLUSION: This study indicated that alcohol consumption is correlated with an increased risk of RA, but further studies are necessary to clarify the exact association.