Exploring the utility of alcohol flushing as an instrumental variable for alcohol intake in Koreans

Previous studies have indicated an association of higher alcohol intake with cardiovascular disease and related traits, but causation has not been definitively established. In this study, the causal effect of alcohol intake on hypertension in 2,011 men and women from the Ansan-Ansung cohort was estimated using an instrumental variable (IV) approach, with both a phenotypic and genotypic instrument for alcohol intake: alcohol flushing and the rs671 genotype (in the alcohol dehydrogenase 2 [ALDH2] gene), respectively. Both alcohol flushing and the rs671 genotype were associated with alcohol intake (difference in alcohol intake with alcohol flushers vs. non-flushers: -9.07 g/day; 95% confidence interval [CI]: -11.12, -7.02; P-value: 8.3 × 10-18 and with the rs671 GA + AA vs. GG genotype: -7.94 g/day; 95% CI: -10.20, -5.69; P-value: 6.1 × 10-12). An increase in alcohol intake, as predicted by both the absence of alcohol flushing and the presence of the rs671 GG genotype in the IV analyses, was associated with an increase in blood pressure in men from this Korean population. In conclusion, this study supports a causal effect of alcohol intake on hypertension and indicated that alcohol flushing may be a valid proxy for the ALDH2 rs671 polymorphism, which influences alcohol intake in this Korean population.