![]() In secondary analyses, we explored the associations of genetically predicted alcohol consumption with possible mediators (blood pressure and serum lipids) and confounders (smoking and education) of the alcohol-CVD associations.įigure 2. 16 By using those SNPs as instrumental variables, we here perform an MR study to investigate the potential causal relationship between alcohol consumption and 8 CVDs, including stroke, coronary artery disease, atrial fibrillation, heart failure, venous thromboembolism, peripheral artery disease, aortic valve stenosis, and abdominal aortic aneurysm. 15 To our knowledge, the association between alcohol consumption and CVD other than stroke and coronary heart disease has not been studied using MR.Ī recent genome-wide association meta-analysis identified multiple SNPs associated with alcohol consumption. 3–6 Results from a recent MR study conducted in a Chinese population showed that increased alcohol consumption instrumented by 2 alcohol-associated SNPs (rs1229984 in ADH1B and rs671 in ALDH2) was associated with higher risk of ischemic stroke and intracerebral hemorrhage but was not associated with myocardial infarction. In a previous MR study in a population of European ancestry, increased alcohol intake instrumented by a single-nucleotide polymorphism (SNP rs1229984) in the ADH1B gene was associated with higher risk of coronary heart disease and ischemic stroke, 14 which contradicts observational findings. 13 MR studies are less vulnerable to bias from confounding, reverse causation, and measurement error compared with conventional observational studies. Mendelian randomization (MR) is an epidemiological technique that utilizes genetic variants that are reliably associated with a potentially modifiable risk factor to determine its causal role for disease risk. Furthermore, self-reported alcohol consumption may be underestimated, leading to measurement error in the assessment of alcohol consumption, which may result in attenuated categorical risk estimates. Observational studies are unable to fully account for confounding and reverse causation bias, and, therefore, causality in the associations of alcohol consumption with different CVDs remains uncertain. 3–6 Data from observational studies on alcohol consumption in relation to other CVDs, including venous thromboembolism, 7, 8 peripheral artery disease, 9 aortic valve stenosis, 10 and abdominal aortic aneurysm, 9, 11, 12 are limited or inconsistent. Observational studies have generally shown that alcohol consumption is positively associated with risk of atrial fibrillation, 2 heart failure, 3 and hemorrhagic stroke, 4 whereas moderate drinking is associated with lower risk of coronary heart disease and ischemic stroke. On a population level, given its widespread nature, it is important to disentangle any risks or benefits of alcohol consumption. Heavy alcohol consumption is an important cause of death and disability, 1 but the association between moderate drinking and cardiovascular disease (CVD) is complex. There was no evidence of associations of genetically predicted alcohol consumption with heart failure (OR, 1.00 P=0.996), venous thromboembolism (OR, 1.04 P=0.810), and aortic valve stenosis (OR, 1.03 P=0.926). These associations were somewhat attenuated in multivariable MR analysis adjusted for smoking initiation. There was some evidence for positive associations of genetically predicted alcohol consumption with coronary artery disease (OR, 1.16 P=0.052), atrial fibrillation (OR, 1.17 P=0.050), and abdominal aortic aneurysm (OR, 2.60 P=0.022) in the inverse variance–weighted analysis. The odds ratios (ORs) per 1-SD increase of log-transformed alcoholic drinks per week were 1.27 ( P=2.87×10 −4) for stroke and 3.05 ( P=2.30×10 −6) for peripheral artery disease in the inverse variance–weighted analysis. Genetically predicted alcohol consumption was consistently associated with stroke and peripheral artery disease across the different analyses. Customer Service and Ordering Information.About Circ: Genomic and Precision Medicine.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB). ![]()
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