Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data

By Michael V. Holmes, C. Dale, L. Zuccolo, R. Silverwood, Yiran Guo, Zheng Ye, D. Prieto-Merino, A. Dehghan, S. Trompet, A. Wong and 145 more. British medical journal, 2014

637 citations recorded by the source corpus.

Objective To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Main outcome measures Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Results Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (−0.88 (−1.19 to −0.56) mm Hg), interleukin-6 levels (−5.2% (−7.8 to −2.4%)), waist circumference (−0.3 (−0.6 to −0.1) cm), and body mass index (−0.17 (−0.24 to −0.10) kg/m2). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). Conclusions Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

Subfields: Epidemiology, Genetics, Pathology and Forensic Medicine

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Citations in the corpus

Alcohol Consumption and Cardiovascular Disease (2020, positive): “14,15 An MR analysis of 261 991 European-descent individuals, including 20 259 coronary heart disease cases, found that each additional alcohol-decreasing allele of rs1229984 in the ADH1B gene was associated with a 10% lower odds of coronary heart disease.”
Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians (2018, background): “6 66 78 79 This is why some studies focus on the association of the genetic variants and outcome, 56 rather than providing a direct quantification of the causal effect scaled to a difference in the exposure of interest.”
Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies (2018, neutral): “HRs for the cardiovascular disease outcomes were generally higher at younger ages, but did not vary substantially by sex, history of diabetes, proatherogenic lipids, BMI, smoking status, or other individual-level characteristics (appendix pp 43–45).”
Machine learning in cardiovascular medicine: are we there yet? (2018, methodology): “MR has been used in a number of cardiovascular studies to causally implicate factors like alcohol intake 44 and LDL cholesterol.”
Mendelian randomization for cardiovascular diseases: principles and applications (2023, positive): “…studies of the association between alcohol consumption and CVD have either used variants in genes that encode enzymes with a key role in alcohol metabolism, 23,24 or all independent genetic variants associated with alcohol consumption at the genome-wide significance level in large consortium data.”
2016 European Guidelines on cardiovascular disease prevention in clinical practice (2017, positive): “Moreover, a recent Mendelian randomization study including analyses from 59 epidemiological studies has shed doubt on any beneficial effect of moderate alcohol consumption [332], suggesting that the lowest risks for CVoutcomes were in abstainers and that any amount of alcohol is associated with elev”