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

To explore the causal effect of long-term alcohol consumption on coronary heart disease risk factors. 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. 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.