Causal effect of alcohol consumption on hyperuricemia using a Mendelian randomization design

Aim: We used a Mendelian randomization analysis to assess the causal effect of alcohol consumption on hyperuricemia in Koreans. Methods: The Korean Cancer Prevention Study-II (KCPS-II) Biobank cohort consisted of 156 701 healthy Korean aged 20 years or older. Clinical data including serum uric acid, alcohol consumption, and other related confounding variables were collected at baseline. The 27 single nucleotide polymorphisms (SNP) including rs671 in aldehyde dehydrogenase 2 (ALDH2) were obtained from a genome-wide association study of alcohol consumption in the KCPS-II Biobank among 11 678 men and women in 2017. Both unweighted and weighted genetic risk score (wGRS) were calculated using 10 SNPs selected based on linkage disequilibrium. Results: As strong instrumental variables, both rs671 and wGRS were associated with an increased amount of alcohol drinking in men and women. Alcohol consumption was also positively associated with hyperuricemia risk in men (P <.001) and women (P =.014). Both rs671 major G allele and wGRS were not associated with hyperuricemia. In Mendelian randomization analysis, the causal relationship between any alcohol consumption and hyperuricemia was found only in men, albeit non-significant after correction for multiple testing. The associations did not change after excluding heavy drinkers or the elderly. Conclusions: These results provide evidence that alcohol consumption is causally associated with risk of hyperuricemia in Korean men and support its role as a risk determinant.