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

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Holmes, Michael V
Dale, Caroline E
Zuccolo, Luisa
Silverwood, Richard J
Guo, Yiran
Ye, Zheng
Prieto-Merino, David
Dehghan, Abbas
Trompet, Stella
Wong, Andrew
Cavadino, Alana
Drogan, Dagmar
Padmanabhan, Sandosh
Li, Shanshan
Yesupriya, Ajay
Leusink, Maarten
Sundstrom, Johan
Hubacek, Jaroslav A
Pikhart, Hynek
Swerdlow, Daniel I
Panayiotou, Andrie G
Borinskaya, Svetlana A
Finan, Chris
Shah, Sonia
Kuchenbaecker, Karoline B
Shah, Tina
Engmann, Jorgen
Folkersen, Lasse
Eriksson, Per
Ricceri, Fulvio
Melander, Olle
Sacerdote, Carlotta
Gamble, Dale M
Rayaprolu, Sruti
Ross, Owen A
McLachlan, Stela
Vikhireva, Olga
Sluijs, Ivonne
Scott, Robert A
Adamkova, Vera
Flicker, Leon
van Bockxmeer, Frank M
Power, Christine
Marques-Vidal, Pedro
Meade, Tom
Marmot, Michael G
Ferro, Jose M
Paulos-Pinheiro, Sofia
Humphries, Steve E
Talmud, Philippa J
Leach, Irene Mateo
Verweij, Niek
Linneberg, Allan
Skaaby, Tea
Doevendans, Pieter A
Cramer, Maarten J
van der Harst, Pim
Klungel, Olaf H
Dowling, Nicole F
Dominiczak, Anna F
Kumari, Meena
Nicolaides, Andrew N
Weikert, Cornelia
Boeing, Heiner
Ebrahim, Shah
Gaunt, Tom R
Price, Jackie F
Lannfelt, Lars
Peasey, Anne
Kubinova, Ruzena
Pajak, Andrzej
Malyutina, Sofia
Voevoda, Mikhail I
Tamosiunas, Abdonas
Maitland-van der Zee, Anke H
Norman, Paul E
Hankey, Graeme J
Bergmann, Manuela M
Hofman, Albert
Franco, Oscar H
Cooper, Jackie
Palmen, Jutta
Spiering, Wilko
de Jong, Pim A
Kuh, Diana
Hardy, Rebecca
Uitterlinden, Andre G
Ikram, M Arfan
Ford, Ian
Hyppönen, Elina
Almeida, Osvaldo P
Wareham, Nicholas J
Khaw, Kay-Tee
Hamsten, Anders
Husemoen, Lise Lotte N
Tjønneland, Anne
Tolstrup, Janne S
Beulens, Joline W J
Verschuren, W M Monique
Onland-Moret, N Charlotte
Hofker, Marten H
Wannamethee, S Goya
Whincup, Peter H
Morris, Richard
Vicente, Astrid M
Watkins, Hugh
Farrall, Martin
Jukema, J Wouter
Meschia, James
Cupples, L Adrienne
Sharp, Stephen J
Fornage, Myriam
Kooperberg, Charles
LaCroix, Andrea Z
Dai, James Y
Lanktree, Matthew B
Siscovick, David S
Jorgenson, Eric
Spring, Bonnie
Coresh, Josef
Li, Yun R
Buxbaum, Sarah G
Schreiner, Pamela J
Ellison, R Curtis
Tsai, Michael Y
Johnson, Andrew D
Hoogeveen, Ron C
Hakonarson, Hakon
Rotter, Jerome I
Boerwinkle, Eric
de Bakker, Paul I W
Kivimaki, Mika
Asselbergs, Folkert W
Sattar, Naveed
Lawlor, Debbie A
Whittaker, John
Davey Smith, George
Psaty, Bruce M
Wilson, James G
Lange, Leslie A
Hamidovic, Ajna
Hingorani, Aroon D
Nordestgaard, Børge G
Bobak, Martin
Leon, David A
Langenberg, Claudia
Palmer, Tom M
Reiner, Alex P
Keating, Brendan J
Dudbridge, Frank
Casas, Juan P
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1136/bmj.g4164Metadata
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Holmes, M. V., C. E. Dale, L. Zuccolo, R. J. Silverwood, Y. Guo, Z. Ye, D. Prieto-Merino, et al. 2014. “Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.” BMJ : British Medical Journal 349 (1): g4164. doi:10.1136/bmj.g4164. http://dx.doi.org/10.1136/bmj.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4091648/pdf/Terms of Use
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