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 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.
Highlights
Alcohol contains components such as ethanol and antioxidants and is considered as a complex modulator to the immune system (Barr et al, 2016)
A recent genome-wide association study (GWAS) conducted in alcohol drinking behavior has identified 99 significant independent loci (Liu et al, 2019), and the GWAS summary statistics for most autoimmune diseases have been made publicly available. Taking advantage of these enormous progresses made in genetic discoveries for complex traits, we aim to perform a large-scale comprehensive study to systemically interrogate the effect of alcohol consumption on a range of common autoimmune inflammatory disorders, leveraging the genetic information available for 1 million individuals of European ancestry
We performed the current study employing a standard framework, that is, a genetic correlation analysis defined as the proportion of variance that two traits share due to genetic causes, and a two-sample Mendelian randomization (MR) analysis, where instrument– exposure and instrument– outcome associations were extracted from two independent non-overlapping sets of participants
Summary
Alcohol contains components such as ethanol and antioxidants and is considered as a complex modulator to the immune system (Barr et al, 2016). In vivo consumption of moderate doses of alcohol enhances phagocytosis and reduces inflammatory cytokine production whereas chronic consumption of large doses inhibits phagocytosis and production of growth factors. For cell-mediated and humoral immunity (adaptive immunity), chronic alcohol abuse significantly reduces both the number and frequency of T lymphocytes, resulting in an increased proportion of memory T cells relative to naïve T cells, which interferes the development of efficacious responses to infection and vaccination. Alcohol modulates the hypothalamic–pituitary– adrenal axis and influences the function of immune cells residing in the central nervous system (CNS) astrocytes and microglia, which tightly regulates the stress response, neuronal function, and CNS homeostasis, in turn affecting immunity (Barr et al, 2016)
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