Is aldehyde dehydrogenase 2 a credible genetic instrument for alcohol use in Mendelian randomization analysis in Southern Chinese men?

BACKGROUND Mendelian randomization studies provide a means of assessing causal relations without interventions, but require valid genetic instruments. We assessed the credibility of aldehyde dehydrogenase 2 (ALDH2) as a genetic instrument for alcohol use in Southern Chinese men. METHODS We genotyped the single nucleotide polymorphism rs671 of ALDH2 in 4867 men from the Guangzhou Biobank Cohort Study. We used linear regression to assess the strength of the association of ALDH2 variants with alcohol use, whether ALDH2 variants were independently associated with socio-economic position or other potential confounders and whether associations of ALDH2 variants with cardiovascular risk factors (systolic and diastolic blood pressure, HDL- and LDL-cholesterol, fasting glucose), triglycerides, body mass index, self reported cardiovascular disease, self-reported ischaemic heart disease, cognitive function (delayed 10-word recall and Mini Mental State Examination score) and liver function (alanine transaminase and aspartate transaminase) were fully mediated by alcohol use. RESULTS The minor allele frequency (A) of ALDH2 was 0.29. The F statistic for ALDH2 variants was 75.0, suggesting that substantial weak instrument bias is unlikely. ALDH2 variants were not associated with socio-economic position, smoking or physical activity. ALDH2 variants were only associated with diastolic blood pressure and HDL-cholesterol, but these genetic associations with blood pressure and HDL-cholesterol were attenuated after adjusting for alcohol use, suggesting the apparent genetic associations were possibly mediated by alcohol use. CONCLUSIONS ALDH2 variants are a credible genetic instrument for Mendelian randomization studies of alcohol use and many attributes of health in Southern Chinese men.