Please use this identifier to cite or link to this item: http://ktisis.cut.ac.cy/handle/10488/4392
Title: Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data
Authors: Holmes, Michael Vaclav 
Dale, Caroline E. 
Zuccolo, Luisa 
Silverwood, Richard J. 
Guo, Yiran 
Ye, Zheng 
Prieto-Merino, David 
Dehghan, Abbas Jan 
Trompet, Stella 
Wong, Andrew 
Cavadino, Alana 
Dudbridge, Frank 
Tsai, Michael 
Hamidovic, Ajna 
Nordestgaard, Borge Grpnne 
Hamsten, Anders 
Wilson, James G. 
Langenberg, Claudia 
Morris, Richard W. 
Engmann, Jorgen E L 
Folkersen, Lasse 
Peasey, Anne E. 
Borinskaya, Svetlana A. 
Mukamal, Kenneth Jay 
Finan, Chris I. 
Whittaker, John C. 
Casas, Juan Pablo 
Sundstrom, Johan 
Farrall, Martin J. 
Keating, Brendan J. 
Swerdlow, Daniel I. 
Lanktree, Matthew B. 
Scott, Robert Alastair Howie 
Hofman, Albert F. 
Paulos-Pinheiro, Sofia 
Rayaprolu, Sruti 
Palmer, Tom M. 
Shah, Sonia H. 
Ricceri, F. 
Spring, Bonnie J. 
Humphries, Steve Eric 
Talmud, Philippa J. 
Hypponen, Elina 
Dominiczak, Anna F D 
Power, Chris 
Panayiotou, Andrie 
Meade, Tom W. 
Hubacek, Jaroslav Alois 
Vikhireva, Olga V. 
Sluijs, Ivonne 
Patel, Sanjay Rajnikant 
Ross, Owen A. 
Flicker, Leon A. 
Sattar, Naveed A. 
Kumari, Meena 
Nicolaides, Andrew N. 
Onland-Moret, N. Charlotte 
Gamble, Dale M. 
Van Der Harst, Pim 
Melander, Olle 
Marmot, Michael Gideon Ideon 
Verweij, Niek 
Smith, George Davey W 
Marques-Vidal, Pedro 
Doevendans, Pieter A F M 
Leon, David A. 
Fornage, Myriam 
Franco, Oscar H. 
Price, Jackie F. 
Van Bockxmeer, Frank M. 
Klungel, Olaf H H 
Boeing, Heiner 
Leusink, Maarten 
Cooper, Jackie A. 
Palmen, Jutta A. 
Buxbaum, Sarah G. 
Norman, Paul E. 
Cramer, Maarten Jan M 
Hankey, Graeme J. 
Linneberg, Allan 
Kubinova, Ruzena 
Pajak, Andrzej 
Pikhart, Hynek 
Lannfelt, Lars 
Tamosiunas, Abdonas 
Eriksson, Per Olof 
Khaw, Kay Tee T 
Boerwinkle, Eric Eric 
Hofker, Marten H. 
Ikram, Mohammad Arfan 
Ebrahim, Shah B J 
Bergmann, Manuela M. 
De Jong, Pim A. 
Sacerdote, Carlotta 
Wannamethee, Sasiwarang Goya Oya 
Whincup, Peter H. 
Lange, Leslie 
Kooperberg, Charles L. 
Tolstrup, Janne Schurmann Churmann 
Maitland-van Der Zee, Anke Hilse 
Beulens, Joline WJ J 
Malyutina, Sofia K. 
Almeida, Osvaldo P De Campos 
Wareham, Nicholas J. 
Adamkova, Vera 
Ford, Ian 
Husemoen, Lise Lotte Nystrup 
Leach, Irene Mateo 
LaCroix, Andrea Z. 
Dai, James Y. 
Drogan, Dagmar 
Uitterlinden, Andre Gerardus 
Cupples, L. Adrienne 
Kuh, Diana 
Verschuren, Wm Monique Monique 
Vicente, Astrid Moura 
Skaaby, Tea 
Rimm, Eric B. 
Jukema, Johan Wouter Outer 
Weikert, Cornelia 
Kuchenbaecker, Karoline B. 
De Bakker, Paul IW W 
Coresh, Josef 
Tjonneland, Anne Marie 
Sharp, Stephen John 
Siscovick, David S. 
Gaunt, Tom R. 
Kivimaki, Mika 
Asselbergs, Folkert W. 
McLachlan, Stela 
Hoogeveen, Ron Cornelis A J M 
Meschia, James F. 
Hakonarson, Hakon H. 
Watkins, Hugh C. 
Schreiner, Pamela J. 
Ellison, Robert Curtis 
Voevoda, Mikhail Ivanovich 
Li, Yun R. 
Redline, Susan S. 
Spiering, Wilko 
Bobak, Martin 
Ferro, Jose Manuel M 
Padmanabhan, Sandosh 
Psaty, Bruce M. 
Jorgenson, Eric M. 
Rotter, Jerome I. 
Lawlor, Debbie A. 
Hardy, Rebecca J. 
Li, Shanshan 
Yesupriya, Ajay 
Dowling, Nicole F. 
Shah, Tina S. 
Reiner, Alexander Paul 
Johnson, Andrew D. 
Keywords: Alcohol abstinence
Alcohol consumption
Alcohol dehydrogenase 1B gene
Issue Date: Jul-2014
Publisher: BMJ Group
Source: BMJ, 2014, Volume 349, Article number g4164
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/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.
URI: http://ktisis.cut.ac.cy/jspui/handle/10488/4392
ISSN: 17561833
DOI: 10.1136/bmj.g4164
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