A causal relationship between alcohol intake and type 2 diabetes mellitus: A two-sample Mendelian randomization study

Background and aims: We investigated whether alcohol intake has a causal relationship with type 2 diabetes mellitus (T2DM) risk in adults of the Korean Genomic Epidemiology Study using two-sample Mendelian randomization (MR) analysis. Methods and results: Daily alcohol intake was calculated based on the type, average amount, and frequency of alcohol consumption for six months before the interview. The participants were divided into low- and high-alcohol intake of 20 g/day. After adjusting for the covariates related to T2DM, the independent genetic variants (instrumental variables) related to alcohol intake were explored by GWAS analysis in a city hospital-based cohort (n = 58,701). SNPs with a significant level of p-value <5 × 10−8 and linkage disequilibrium of r2 < 0.001 were retrieved. MR methods were used to analyze the causality between alcohol intake and the T2DM risk, and the heterogeneity and leave-one-out sensitivity analyses were conducted in Ansan/Ansung plus rural cohorts (n = 13,598). High alcohol intake increased T2DM risk when the inverse-variance weighted (P = 0.012) and weighted median (P = 0.034) methods were used, but not when the MR-Egger method was used. No significant heterogeneity and horizontal pleiotropy between alcohol intake and T2DM were detected. A single genetic variant did not affect the causal association in a leave-one-out sensitivity analysis. Conclusion: This study supports that heavy alcohol intake appears to be causally associated with T2DM risk.