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

• Main Authors: Xia Jiang, Zhaozhong Zhu, Ali Manouchehrinia, Tomas Olsson, Lars Alfredsson, Ingrid Kockum
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-06-01
• Series: Frontiers in Genetics
• Subjects: Mendelian Randomization (MR); alcohol consumption amount; excessive drinking; autoimmune disease; genetic correlation; large-scale genetic analysis
• Online Access: https://www.frontiersin.org/articles/10.3389/fgene.2021.687745/full

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 (rg = −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.