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

Michael V. Holmes(University College London), Caroline Dale(London School of Hygiene & Tropical Medicine), Luisa Zuccolo(MRC Epidemiology Unit), Richard J. Silverwood(University of London), Yanfei Guo(BGI Group (China)), Z. Ye(Addenbrooke's Hospital), David Prieto‐Merino(London School of Hygiene & Tropical Medicine), Abbas Dehghan(Erasmus MC), Stella Trompet(Leiden University Medical Center), Andrew Wong(MRC Unit for Lifelong Health and Ageing), Alana Cavadino(University College London), Dagmar Drogan(German Institute of Human Nutrition), Sandosh Padmanabhan(University of Glasgow), Simon Li(Harvard University), Ajay Yesupriya(Centers for Disease Control and Prevention), Maarten Leusink(Utrecht University), Johan Sundström(Uppsala University Hospital), Jaroslav A. Hubáček(Institute of Clinical and Experimental Medicine), Hynek Pikhart(University College London), Daniel I. Swerdlow(University College London), Andrie G. Panayiotou(Cyprus University of Technology), S. A. Borinskaya(Vavilov Institute of General Genetics), Chris Finan(University College London), Sonia Shah(University College London), Karoline Kuchenbaecker(University of Cambridge), Tina Shah(University College London), Jorgen Engmann(University College London), Lasse Folkersen(Karolinska Institutet), Per Eriksson(Karolinska Institutet), Fulvio Ricceri(Piedmont Reference Center for Epidemiology and Cancer Prevention), Olle Melander(Lund University), Carlotta Sacerdote(Piedmont Reference Center for Epidemiology and Cancer Prevention), Dale M. Gamble(WinnMed), Sruti Rayaprolu(Mayo Clinic in Florida), Owen A. Ross(Mayo Clinic in Florida), S. McLachlan(University of Edinburgh), Olga Vikhireva(University College London), Ivonne Sluijs(University Medical Center Utrecht), R.A. Scott(Addenbrooke's Hospital), Věra Adámková(Institute of Clinical and Experimental Medicine), Leon Flicker(The University of Western Australia), F. M. van Bockxmeer(The University of Western Australia), Chris Power(University College London), Pedro Marques‐Vidal, T W Meade(London School of Hygiene & Tropical Medicine), Michael Marmot(University College London), José M. Ferro(University of Lisbon), S. Paulos-Pinheiro(University of Lisbon), Steve E. Humphries(University College London), Philippa J. Talmud(University College London), Irene Mateo Leach(University Medical Center Groningen), Niek Verweij(University Medical Center Groningen), Allan Linneberg(Glostrup Hospital), Tea Skaaby(Glostrup Hospital), Pieter A. Doevendans(University Medical Center Utrecht), Maarten J. Cramer(University Medical Center Utrecht), Pim van der Harst(University Medical Center Groningen), Olaf H. Klungel(Utrecht University), Nicole F. Dowling(Centers for Disease Control and Prevention), Anna F. Dominiczak(University of Glasgow), Meena Kumari(University College London), Andrew Nicolaides(University of Cyprus), Cornelia Weikert(German Institute of Human Nutrition), Heiner Boeing(German Institute of Human Nutrition), Shah Ebrahim(London School of Hygiene & Tropical Medicine), Tom R. Gaunt(MRC Epidemiology Unit), Jackie F. Price(University of Edinburgh), L. Lannfelt(Uppsala University Hospital), Anne Peasey(University College London), Růžena Kubínová(National Institute of Public Health), A. Pajak(Jagiellonian University), Sofia Malyutina(Novosibirsk State Medical University), M. I. Voevoda(Novosibirsk State Medical University), Algirdas Tamošiūnas(Lithuanian University of Health Sciences), Anke H. Maitland‐van der Zee(Utrecht University), Paul E. Norman(The University of Western Australia), Graeme J. Hankey(The University of Western Australia), Michael Bergmann(German Institute of Human Nutrition), Amy Hofman(Erasmus MC), Oscar H. Franco(Erasmus MC), J. Cooper(University College London), Jutta Palmen(University College London), Wilko Spiering(University Medical Center Utrecht), Pim A. de Jong(University Medical Center Utrecht), Diana Kuh(MRC Unit for Lifelong Health and Ageing), Rebecca Hardy(MRC Unit for Lifelong Health and Ageing), André G. Uitterlinden(Erasmus MC), M. Arfan Ikram(Erasmus MC), Ian Ford(University of Glasgow), Elina Hyppönen(University of South Australia), Osvaldo P. Almeida(The University of Western Australia), Nicholas J. Wareham(Addenbrooke's Hospital), K.-T. Khaw(University of Cambridge), Anders Hamsten(Karolinska University Hospital), Lise Lotte N. Husemoen(Glostrup Hospital), Anne Tjønneland(Danish Cancer Society), Janne Schurmann Tolstrup(University of Southern Denmark), Eric B. Rimm(Brigham and Women's Hospital), Joline W. J. Beulens(University Medical Center Utrecht), W. M. Monique Verschuren(National Institute for Public Health and the Environment), N. Charlotte Onland‐Moret(University Medical Center Utrecht), Marten H. Hofker(University Medical Center Groningen), S. Goya Wannamethee(University College London), Peter H. Whincup(St George's, University of London), Richard Morris(University College London), Astrid M. Vicente(National Institute of Health Dr. Ricardo Jorge), Hugh Watkins(Centre for Human Genetics), Martin Farrall(Centre for Human Genetics), J. Wouter Jukema(Leiden University Medical Center), James F. Meschia(WinnMed), L. Adrienne Cupples(Boston University), Stephen J. Sharp(Addenbrooke's Hospital), M. Fornage(The University of Texas Health Science Center at Houston), Charles Kooperberg(Fred Hutch Cancer Center), Andrea Z. LaCroix(Fred Hutch Cancer Center), Jiyan Dai(Fred Hutch Cancer Center), Matthew B. Lanktree(McMaster University), David S. Siscovick(New York Academy of Medicine), Eric Jorgenson(Kaiser Permanente), Bonnie Spring(Northwestern University), Josef Coresh(Johns Hopkins University), Leslie A. Lange(Children's Hospital of Philadelphia), Sarah G. Buxbaum(Jackson State University), Pamela J. Schreiner(University of Minnesota), R. Curtis Ellison(Boston University), Michael Y. Tsai(University of Minnesota), Sanjay R. Patel(Boston University), Susan Redline(Boston University), Andrew D. Johnson(National Heart Lung and Blood Institute), Ron C. Hoogeveen(Baylor College of Medicine), H. Hakonarson(Children's Hospital of Philadelphia), Jerome I. Rotter(The Lundquist Institute), Eric Boerwinkle(The University of Texas Health Science Center at Houston), Paul I. W. de Bakker(University Medical Center Utrecht), Mika Kivimäki(University College London), Folkert W. Asselbergs(University Medical Center Utrecht), Naveed Sattar(University of Glasgow), Debbie A. Lawlor(MRC Epidemiology Unit), John C. Whittaker(University of London), George Davey Smith(MRC Epidemiology Unit), K. Mukamal(Beth Israel Deaconess Medical Center), Bruce M. Psaty(Group Health Cooperative), James Wilson(Jackson Memorial Hospital), Leslie A. Lange(University of North Carolina at Chapel Hill), Ajna Hamidovic(University of New Mexico), Aroon D. Hingorani(University College London), Børge G. Nordestgaard(University of Copenhagen), Martin Bobák(University College London), David A. Leon(London School of Hygiene & Tropical Medicine), Claudia Langenberg(Addenbrooke's Hospital), Tom Palmer(University of Warwick), Alex P. Reiner(Fred Hutch Cancer Center), Brendan J. Keating(Children's Hospital of Philadelphia), Frank Dudbridge(London School of Hygiene & Tropical Medicine), J. P. Casas(London School of Hygiene & Tropical Medicine)
BMJ
July 10, 2014
10.1136/bmj.g4164
Cited by 676Open Access
Full Text

Abstract

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.

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