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Purpose:  Observational studies have suggested a protective effect of alcohol intake with autoimmune disorders, which was not supported by Mendelian randomization (MR) analyses that used only a few (<20) instrumental variables.   Methods:  We systemically interrogated a putative causal relationship between alcohol consumption and four common autoimmune disorders, using summary-level data from the largest genome-wide association study (GWAS) conducted on inflammatory bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE). We quantified the genetic correlation to examine a shared genetic similarity. We constructed a strong instrument using 99 genetic variants associated with drinks per week and applied several two-sample MR methods. We additionally incorporated excessive drinking as reflected by alcohol use disorder identification test score.   Results:  We observed a negatively shared genetic basis between alcohol intake and autoimmune disorders, although none was significant ( r   g   = −0.07 to −0.02). For most disorders, genetically predicted alcohol consumption was associated with a slightly (10–25%) decreased risk of onset, yet these associations were not significant. Meta-analyzing across RA, MS, and IBD, the three Th1-related disorders yielded to a marginally significantly reduced effect [OR = 0.70 (0.51–0.95),  P  = 0.02]. Excessive drinking did not appear to reduce the risk of autoimmune disorders.   Conclusions:  With its greatly augmented sample size and substantially improved statistical power, our MR study does not convincingly support a beneficial role of alcohol consumption in each individual autoimmune disorder. Future studies may be designed to replicate our findings and to understand a causal effect on disease prognosis.

Alcohol Consumption and Risk of Common Autoimmune Inflammatory Diseases—Evidence From a Large-Scale Genetic Analysis Totaling 1 Million Individuals