Alcohol Consumption and Cardiovascular Disease: A Mendelian Randomization Study - PubMed (original) (raw)

Clinical Trial

Alcohol Consumption and Cardiovascular Disease: A Mendelian Randomization Study

Susanna C Larsson et al. Circ Genom Precis Med. 2020 Jun.

Abstract

Background: The causal role of alcohol consumption for cardiovascular disease remains unclear. We used Mendelian randomization (MR) to predict the effect of alcohol consumption on 8 cardiovascular diseases.

Methods: Up to 94 single-nucleotide polymorphisms were used as instrumental variables for alcohol consumption. Genetic association estimates for cardiovascular diseases were obtained from large-scale consortia and UK Biobank. Analyses were conducted using the inverse variance-weighted, weighted median, MR-PRESSO, MR-Egger, and multivariable MR methods.

Results: Genetically predicted alcohol consumption was consistently associated with stroke and peripheral artery disease across the different analyses. The odds ratios (ORs) per 1-SD increase of log-transformed alcoholic drinks per week were 1.27 ([95% CI, 1.12-1.45] _P_=2.87×10-4) for stroke and 3.05 ([95% CI, 1.92-4.85] _P_=2.30×10-6) for peripheral artery disease in the inverse variance-weighted analysis. There was some evidence for positive associations of genetically predicted alcohol consumption with coronary artery disease (OR, 1.16 [95% CI, 1.00-1.36]; _P_=0.052), atrial fibrillation (OR, 1.17 [95% CI, 1.00-1.37]; _P_=0.050), and abdominal aortic aneurysm (OR, 2.60 [95% CI, 1.15-5.89]; _P_=0.022) in the inverse variance-weighted analysis. These associations were somewhat attenuated in multivariable MR analysis adjusted for smoking initiation. There was no evidence of associations of genetically predicted alcohol consumption with heart failure (OR, 1.00 [95% CI, 0.68-1.47]; _P_=0.996), venous thromboembolism (OR, 1.04 [95% CI, 0.77-1.39]; _P_=0.810), and aortic valve stenosis (OR, 1.03 [95% CI, 0.56-1.90]; _P_=0.926).

Conclusions: This study provides evidence of a causal relationship between higher alcohol consumption and increased risk of stroke and peripheral artery disease. The causal role of alcohol consumption for other cardiovascular diseases requires further research.

Keywords: alcohol drinking; cardiovascular diseases; coronary artery disease; odds ratio; peripheral artery disease; stroke.

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Figures

Figure 1.

Figure 1.

Summary of the data sources for this study and the assumptions for the Mendelian randomization design. Broken lines represent potential pleiotropic or direct causal effects between variables that would violate the Mendelian randomization assumptions. AFGen indicates Atrial Fibrillation Consortium; CAD, coronary artery disease; CARDIoGRAMplusC4D, Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Plus the Coronary Artery Disease Genetics Consortium; GSCAN, GWAS and Sequencing Consortium of Alcohol and Nicotine Use; GWAS, genome-wide association study; ISGC, International Stroke Genetics Consortium; SNP, single-nucleotide polymorphism; SSGAC, Science Genetic Association Consortium; and UKBB, UK Biobank. *Reported are the outcome and within parenthesis, the number of cases and noncases and data source(s).

Figure 2.

Figure 2.

Associations of alcohol consumption instrumented by the full set of single-nucleotide polymorphisms with blood pressure and lipids. The effect estimates are per SD increase of log-transformed alcoholic drinks per week, and results are based on the random-effects inverse variance–weighted method. DBP indicates diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; OR, odds ratio; SBP, systolic blood pressure; and TG, triglyceride.

Figure 3.

Figure 3.

Associations of alcohol consumption instrumented by the full set of single-nucleotide polymorphisms with CVD. Odds ratios (ORs) are per SD increase of log-transformed alcoholic drinks per week, and results are based on the random-effects inverse variance–weighted (IVW) method and multivariable Mendelian randomization (MVMR) analysis adjusted for smoking initiation.

Figure 4.

Figure 4.

Associations of alcohol consumption instrumented by the full set of single-nucleotide polymorphisms with stroke types in the MEGASTROKE Consortium, UK Biobank, and International Stroke Genetics Consortium (ISGC). Odds ratios (ORs) are per SD increase of log-transformed alcoholic drinks per week, and results are based on the random-effects inverse variance–weighted method.

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