AUTHOR=Jiang Xia , Zhu Zhaozhong , Manouchehrinia Ali , Olsson Tomas , Alfredsson Lars , Kockum Ingrid TITLE=Alcohol Consumption and Risk of Common Autoimmune Inflammatory Diseases—Evidence From a Large-Scale Genetic Analysis Totaling 1 Million Individuals JOURNAL=Frontiers in Genetics VOLUME=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.687745 DOI=10.3389/fgene.2021.687745 ISSN=1664-8021 ABSTRACT=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 GWAS conducted on inflammatory bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS) and systemic lupus erythematosus (SLE). We quantified the genetic correlation to understand a shared similarity. We constructed a strong instrument using 99 genetic variants associated with drinks/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 negatively shared genetic basis between alcohol intake and autoimmune disorders although none was significant (rg -0.07- -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 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 impact on disease prognosis.