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

作者：Michael V. Holmes, Caroline Dale, Luisa Zuccolo, Richard J. Silverwood, Yanfei Guo, Z. Ye, David Prieto‐Merino, Abbas Dehghan, Stella Trompet, Andrew Wong, Alana Cavadino, Dagmar Drogan, Sandosh Padmanabhan, Simon Li, Ajay Yesupriya, Maarten Leusink, Johan Sundström, Jaroslav A. Hubáček, Hynek Pikhart, Daniel I. Swerdlow, Andrie G. Panayiotou, S. A. Borinskaya, Chris Finan, Sonia Shah, Karoline Kuchenbaecker, Tina Shah, Jorgen Engmann, Lasse Folkersen, Per Eriksson, Fulvio Ricceri, Olle Melander, Carlotta Sacerdote, Dale M. Gamble, Sruti Rayaprolu, Owen A. Ross, S. McLachlan, Olga Vikhireva, Ivonne Sluijs, R.A. Scott, Věra Adámková, Leon Flicker, F. M. van Bockxmeer, Chris Power, Pedro Marques‐Vidal, T W Meade, Michael Marmot, José M. Ferro, S. Paulos-Pinheiro, Steve E. Humphries, Philippa J. Talmud, Irene Mateo Leach, Niek Verweij, Allan Linneberg, Tea Skaaby, Pieter A. Doevendans, Maarten J. Cramer, Pim van der Harst, Olaf H. Klungel, Nicole F. Dowling, Anna F. Dominiczak, Meena Kumari, Andrew Nicolaides, Cornelia Weikert, Heiner Boeing, Shah Ebrahim, Tom R. Gaunt, Jackie F. Price, L. Lannfelt, Anne Peasey, Růžena Kubínová, A. Pajak, Sofia Malyutina, M. I. Voevoda, Algirdas Tamošiūnas, Anke H. Maitland‐van der Zee, Paul E. Norman, Graeme J. Hankey, Michael Bergmann, Amy Hofman, Oscar H. Franco, J. Cooper, Jutta Palmen, Wilko Spiering, Pim A. de Jong, Diana Kuh, Rebecca Hardy, André G. Uitterlinden, M. Arfan Ikram, Ian Ford, Elina Hyppönen, Osvaldo P. Almeida, Nicholas J. Wareham, K.-T. Khaw, Anders Hamsten, Lise Lotte N. Husemoen, Anne Tjønneland, Janne Schurmann Tolstrup, Eric B. Rimm, Joline W. J. Beulens, W. M. Monique Verschuren, N. Charlotte Onland‐Moret, Marten H. Hofker, S. Goya Wannamethee, Peter H. Whincup, Richard Morris, Astrid M. Vicente, Hugh Watkins, Martin Farrall, J. Wouter Jukema, James F. Meschia, L. Adrienne Cupples, Stephen J. Sharp, M. Fornage, Charles Kooperberg, Andrea Z. LaCroix, Jiyan Dai, Matthew B. Lanktree, David S. Siscovick, Eric Jorgenson, Bonnie Spring, Josef Coresh, Y. R. Li, Sarah G. Buxbaum, Pamela J. Schreiner, R. Curtis Ellison, Michael Y. Tsai, Sanjay R. Patel, Susan Redline, Andrew D. Johnson, Ron C. Hoogeveen, H. Hakonarson, Jerome I. Rotter, Eric Boerwinkle, Paul I. W. de Bakker, Mika Kivimäki, Folkert W. Asselbergs, Naveed Sattar, Debbie A. Lawlor, John C. Whittaker, George Davey Smith, K. Mukamal, Bruce M. Psaty, James Wilson, Leslie A. Lange, Ajna Hamidovic, Aroon D. Hingorani, Børge G. Nordestgaard, Martin Bobák, David A. Leon, Claudia Langenberg, Tom Palmer, Alex P. Reiner, Brendan J. Keating, Frank Dudbridge, J. P. Casas · 发表于：BMJ · 年份：2014 · DOI：10.1136/bmj.g4164 · 被引用次数：689 · 研究领域：Alcohol Consumption and Health Effects、Substance Abuse Treatment and Outcomes、Genetic Associations and Epidemiology

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...