Examining the causal association between moderate alcohol consumption and cardiovascular risk factors in the Taiwan Biobank: a Mendelian randomization analysis

Background: The Mendelian randomization approach uses genetic variants as instrumental variables to study the causal association between the risk factors and health outcomes of interest. We aimed to examine the relation between alcohol consumption and cardiovascular risk factors using two genetic variants as instrumental variables: alcohol dehydrogenase 1B (ADH1B) rs1229984 and aldehyde dehydrogenase 2 (ALDH2) rs671. Methods: Using data collected in the Taiwan Biobank—an ongoing, prospective, population-based cohort study—our analysis included 129,032 individuals (46,547 men and 82,485 women) with complete data on ADH1B rs1229984 and ALDH2 rs671 genotypes and alcohol drinking status. We conducted instrumental variables regression analysis to examine the relationship between alcohol drinking and body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, glycated hemoglobin (HbA1c), triglycerides, high-density lipoprotein cholesterol (HDLc), and low-density lipoprotein cholesterol (LDLc). Results: In the rs1229984-instrumented analysis, alcohol drinking was only associated with higher levels of SBP in men and lower levels of DBP in women. In the rs671-instrumented analysis, alcohol drinking was associated with higher levels of BMI, SBP, DBP, fasting glucose, triglycerides, HDLc and lower levels of LDLc in men; alcohol drinking was associated with higher levels of HDLc and lower levels of SBP, HbA1c, and triglycerides in women. Conclusion: Using Mendelian randomization analysis, some of our study results among men echoed findings from the previous systematic review, suggesting that alcohol drinking may be causally associated with higher levels of BMI, SBP, DBP, fasting glucose, triglycerides, HDLc, and lower levels of LDLc. Although alcohol drinking is beneficial to a few cardiovascular risk factors, it is detrimental to many others. The assumptions that underlie the Mendelian randomization approach should also be carefully examined when interpreting findings from such studies.