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

  • Meiling Liu
    Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, 31499, Republic of Korea
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  • Sunmin Park
    Corresponding author. Food and Nutrition, Hoseo University, 165 Sechul-Ri, BaeBang-Yup, Asan-Si, ChungNam-Do, 31149, South Korea.
    Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan, 31499, Republic of Korea
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      • Alcohol intake (≥20 g/day) was positively associated with type 2 diabetes (T2DM) using Korean cohorts in a two-sample MR.
      • No significant heterogeneity or horizontal pleiotropy between alcohol intake and T2DM was noted.
      • Heavy alcohol intake appeared to exert a positive causal relationship to T2DM risk in Asians.
      • These findings highlight that reducing alcohol consumption may be a preventive strategy for avoiding T2DM among alcoholics.


      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.


      This study supports that heavy alcohol intake appears to be causally associated with T2DM risk.



      T2DM (type 2 diabetes mellitus), GWAS (genome-wide association studies), MR (Mendelian randomization), KoGES (Korean Genomic Epidemiology Study), hs-CRP (high-sensitive C-reactive protein), BMI (body mass index), HbA1c (hemoglobin A1c), SQFFQ (semi-quantitative food frequency questionnaire), HWE (Hardy-Weinberg Equilibrium), MAF (minor alleles frequency), λGC (genome inflation factor lambda), Q-Q (quantile-quantile), IVW (inverse variance weighting), SNP (single nucleotide polymorphism), HDL (high-density lipoprotein)
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