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

Michael V. Holmes, Caroline E. Dale, Luisa Zuccolo, Richard J. Silverwood, Yiran Guo, Zheng Ye, David Prieto-Merino, Abbas Dehghan, Stella Trompet, Andrew Wong, Alana Cavadino, Dagmar Drogan, Sandosh Padmanabhan, Shanshan Li, Ajay Yesupriya, Maarten Leusink, Johan Sundstrom, Jaroslav A. Hubacek, Hynek Pikhart, Daniel I. SwerdlowAndrie G. Panayiotou, Svetlana A. Borinskaya, Chris Finan, Sonia Shah, Karoline B. Kuchenbaecker, Tina Shah, Jorgen Engmann, Lasse Folkersen, Per Eriksson, Fulvio Ricceri, Olle Melander, Carlotta Sacerdote, Dale M. Gamble, Sruti Rayaprolu, Owen A. Ross, Stela McLachlan, Olga Vikhireva, Ivonne Sluijs, Robert A. Scott, Vera Adamkova, Leon Flicker, Frank M. Van Bockxmeer, Christine Power, Pedro Marques-Vidal, Irene Mateo Leach, Niek Verweij, Pim Van der Harst, Meena Kumari, Marten H. Hofker, Folkert W. Asselbergs, IMPROVE Study Grp, InterAct Consortium

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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/m(2)). 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.

Original languageEnglish
Article number4164
Number of pages16
JournalBMJ-British Medical Journal
Publication statusPublished - 10-Jul-2014



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