Rosoff, D. B. | Search bioRxiv

bioRxiv2019

Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization

Alcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.

genomics↗

bioRxiv2019

Educational attainment causally impacts drinking behaviors and risk for alcohol dependence: results from a two-sample Mendelian randomization study in ~ 780,000 study participants

BackgroundObservational studies suggest that lower educational attainment may be associated with risky alcohol consumption behaviors. However, these findings may be biased by confounding and reverse causality. Using two-sample Mendelian randomization (MR), we can determine whether education is causally related to alcohol consumption behaviors and alcohol dependence (AD). MethodsWe performed two-sample MR using summary statistics from recent genome-wide association studies (GWAS) in 784,726 study participants to assess the causal effects of educational attainment on alcohol consumption behaviors, including intake frequency, total weekly drinks, beverage preferences, whether alcohol is consumed with meals, as well as AD risk. Of 53 independent (linkage disequilibrium R2=0.001, kb distance<10,000) nucleotide polymorphisms (SNPs) that predict educational attainment, and after removal of palindromes with intermediate allele frequency, 51 were present in the alcohol consumption behaviors, and 44 were present in the AD GWAS. Complementary MR techniques accommodating different assumptions about genetic pleiotropy (inverse variance weighted (IVW), Egger, weighted median, and weighted mode MR) tested the sensitivity of our results. ResultsWe found strong evidence of a causal effect between years of education and alcohol consumption behaviors generally. Higher educational attainment decreased alcohol intake frequency (IVW odds ratio (ORIVW), 0.718, 95% CI, 0.673-0.765, PIVW=4.62E-24), as well as weekly distilled spirits intake (ORIVW, 0.874, 95% CI, 0.833-0.917, PIVW=3.91E-08), and weekly beer plus cider intake (ORIVW, 0.837, 95% CI, 0.805-0.869, P=5.58E-20), but increased weekly white wine (ORIVW, 1.220, 95% CI, 1.172-1.269, PIVW=7.96E-23), red wine (ORIVW, 1.227, 95% CI, 1.174-1.282, PIVW=6.67E-20), and fortified wine intake (ORIVW, 1.051, 95% CI, 1.027-1.075, PIVW] =1.87E-07). We also found evidence educational attainment reduced AD risk (ORIVW.508, 95% CI, .315-.819, PIVW=5.51E-03). We found no evidence for total weekly consumption (ORIVW.508, 95% CI.315-.819, PIVW=5.51E-03). Consistency of results across complementary MR methods strengthens our causal inferences. ConclusionsOur findings show low educational attainment is causally associated with increased alcohol consumption frequency, increased preference for beer, cider, and spirits, and AD risk, indicating a potential mechanism explaining reported associations between educational attainment and adverse health outcomes, including cardiovascular disease. These findings suggest increased educational attainment might be a useful prevention strategy to reduce risky alcohol behaviors and AD.

epidemiology↗