Exploring causal associations between alcohol and coronary heart disease risk factors: findings from a Mendelian randomization study in the Copenhagen General Population Study

AIMS: To explore the causal effect of long-term alcohol consumption on coronary heart disease risk factors. METHODS AND RESULTS: We used variants in ADH1B and ADH1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on body mass index (BMI), blood pressure (BP), lipids, fibrinogen, and glucose. Analyses were undertaken in 54 604 Danes (mean age 56 years). Both confounder-adjusted multivariable and IV analyses suggested that a greater alcohol consumption among those who drank any alcohol resulted in a higher BP mean difference in SBP per doubling of alcohol consumption among drinkers: 0.76 mmHg (95% CI: 0.63, 0.90) from multivariable analyses and 0.94 mmHg (-3.03, 4.69) from IV analyses; P-value for difference in these results = 0.95. The positive association of alcohol with HDLc in the multivariable analyses 4.9% (4.7, 5.1) appeared stronger than in the IV analyses 1.5% (-4.5, 7.4), and the weak inverse association with fibrinogen in the multivariable analysis -2.0% (-2.1, -1.8) was not present in the IV analyses 0.6% (-3.8, 5.0), but statistically the results for both of these could not be reliably distinguished from each other (P-values 0.21 and 0.32, respectively). The weak inverse association of alcohol with BMI -0.13 kg/m(2) (-0.16, -0.10) and with triglycerides -0.4% (-0.7, 0.4) in multivariable analyses were in contrast to the strong positive association of alcohol with BMI 1.37 kg/m(2) (0.59, 2.15) and the strong inverse association with triglycerides -14.9% (-25.6, -4.3) in IV analyses; P = 0.006 and 0.01, respectively, for difference between the two. Alcohol was not associated with non-HDLc or glucose. CONCLUSION: Our results show adverse effects of long-term alcohol consumption on BP and BMI. We also found novel evidence for a potentially beneficial effect on triglyceride levels, which needs further replication.