Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study

• Published in: PLoS medicine 2020-12, Vol.17 (12), p.e1003410
• Main Authors: Rosoff, Daniel B, Davey Smith, George, Mehta, Nehal, Clarke, Toni-Kim, Lohoff, Falk W
• Format: Article
• Language: English
• Subjects: Alcohol Drinking - adverse effects; Alcohol Drinking - epidemiology; Alcohol Drinking - genetics; Alcohol use; Alcoholic beverages; Apolipoprotein B; Beer; Biology and Life Sciences; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Champagne; Cholesterol; Cider; Consortia; Coronary artery; Coronary artery disease; Coronary vessels; Drinking of alcoholic beverages; Epidemiology; Genetic aspects; Genetic Predisposition to Disease; Genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genotype & phenotype; Health aspects; Heart Disease Risk Factors; Heart diseases; High density lipoprotein; Humans; Lipids; Lipoproteins; Low density lipoprotein; Medicine and Health Sciences; Mendelian Randomization Analysis; Multivariate Analysis; Phenotypes; Polymorphism, Single Nucleotide; Risk Assessment; Risk factors; Single-nucleotide polymorphism; Smoking; Social Sciences; Stroke; Tobacco; Tobacco Use - adverse effects; Tobacco Use - epidemiology; Tobacco Use - genetics; Triglycerides; Wine
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.1003410

Alcohol consumption and smoking, 2 major risk factors for cardiovascular disease (CVD), often occur together. The objective of this study is to use a wide range of CVD risk factors and outcomes to evaluate potential total and direct causal roles of alcohol and tobacco use on CVD risk factors and events. Using large publicly available genome-wide association studies (GWASs) (results from more than 1.2 million combined study participants) of predominantly European ancestry, we conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent impact of alcohol consumption and smoking on a wide range of CVD risk factors and outcomes. Multiple sensitivity analyses, including complementary Mendelian randomization (MR) methods, and secondary alcohol consumption and smoking datasets were used. SVMR showed genetic predisposition for alcohol consumption to be associated with CVD risk factors, including high-density lipoprotein cholesterol (HDL-C) (beta 0.40, 95% confidence interval (CI), 0.04-0.47, P value = 1.72 × 10-28), triglycerides (TRG) (beta -0.23, 95% CI, -0.30, -0.15, P value = 4.69 × 10-10), automated systolic blood pressure (BP) measurement (beta 0.11, 95% CI, 0.03-0.18, P value = 4.72 × 10-3), and automated diastolic BP measurement (beta 0.09, 95% CI, 0.03-0.16, P value = 5.24 × 10-3). Conversely, genetically predicted smoking was associated with increased TRG (beta 0.097, 95% CI, 0.014-0.027, P value = 6.59 × 10-12). Alcohol consumption was also associated with increased myocardial infarction (MI) and coronary heart disease (CHD) risks (MI odds ratio (OR) = 1.24, 95% CI, 1.03-1.50, P value = 0.02; CHD OR = 1.21, 95% CI, 1.01-1.45, P value = 0.04); however, its impact was attenuated in MVMR adjusting for smoking. Conversely, alcohol maintained an association with coronary atherosclerosis (OR 1.02, 95% CI, 1.01-1.03, P value = 5.56 × 10-4). In comparison, after adjusting for alcohol consumption, smoking retained its association with several CVD outcomes including MI (OR = 1.84, 95% CI, 1.43, 2.37, P value = 2.0 × 10-6), CHD (OR = 1.64, 95% CI, 1.28-2.09, P value = 8.07 × 10-5), heart failure (HF) (OR = 1.61, 95% CI, 1.32-1.95, P value = 1.9 × 10-6), and large artery atherosclerosis (OR = 2.4, 95% CI, 1.41-4.07, P value = 0.003). Notably, using the FinnGen cohort data, we were able to replicate the association between smoking and several CVD outcomes including MI (OR