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

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posted on 13.05.2019, 08:57 by MV Holmes, CE Dale, L Zuccolo, RJ Silverwood, Y Guo, Z Ye, D Prieto-Merino, A Dehghan, S Trompet, A Wong, A Cavadino, D Drogan, S Padmanabhan, S Li, A Yesupriya, M Leusink, J Sundstrom, JA Hubacek, H Pikhart, DI Swerdlow, AG Panayiotou, SA Borinskaya, C Finan, S Shah, KB Kuchenbaecker, T Shah, J Engmann, L Folkersen, P Eriksson, F Ricceri, O Melander, C Sacerdote, DM Gamble, S Rayaprolu, OA Ross, S McLachlan, O Vikhireva, I Sluijs, RA Scott, V Adamkova, L Flicker, FMV Bockxmeer, C Power, P Marques-Vidal, T Meade, MG Marmot, JM Ferro, S Paulos-Pinheiro, SE Humphries, PJ Talmud, I Mateo Leach, N Verweij, A Linneberg, T Skaaby, PA Doevendans, MJ Cramer, P van der Harst, OH Klungel, NF Dowling, AF Dominiczak, M Kumari, AN Nicolaides, C Weikert, H Boeing, S Ebrahim, TR Gaunt, JF Price, L Lannfelt, A Peasey, R Kubinova, A Pajak, S Malyutina, MI Voevoda, A Tamosiunas, AH Maitland-van der Zee, PE Norman, GJ Hankey, MM Bergmann, A Hofman, OH Franco, J Cooper, J Palmen, W Spiering, PA de Jong, D Kuh, R Hardy, AG Uitterlinden, MA Ikram, I Ford, E Hyppönen, OP Almeida, NJ Wareham, K-T Khaw, A Hamsten, LLN Husemoen, A Tjønneland, JS Tolstrup, E Rimm, JWJ Beulens, WMM Verschuren, NC Onland-Moret, MH Hofker, SG Wannamethee, PH Whincup, R Morris, AM Vicente, H Watkins, M Farrall, JW Jukema, J Meschia, LA Cupples, SJ Sharp, M Fornage, C Kooperberg, AZ LaCroix, JY Dai, MB Lanktree, DS Siscovick, E Jorgenson, B Spring, J Coresh, YR Li, SG Buxbaum, PJ Schreiner, RC Ellison, MY Tsai, SR Patel, S Redline, AD Johnson, RC Hoogeveen, H Hakonarson, JI Rotter, E Boerwinkle, PIW de Bakker, M Kivimaki, FW Asselbergs, N Sattar, DA Lawlor, J Whittaker, G Davey Smith, K Mukamal, BM Psaty, JG Wilson, LA Lange, A Hamidovic, AD Hingorani, BG Nordestgaard, M Bobak, DA Leon, C Langenberg, TM Palmer, AP Reiner, BJ Keating, F Dudbridge, JP Casas, InterAct Consortium
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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CCBYNC Open access Research Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4164 (Published 10 July 2014) Cite this as: BMJ 2014;349:g4164 Article Related content Metrics Responses Peer review Michael V Holmes, assistant professor (joint first author)123, Caroline E Dale, research fellow (joint first author)4, Luisa Zuccolo, population health scientist fellow5, Richard J Silverwood, lecturer in medical statistics46, Yiran Guo, research associate78, Zheng Ye, investigator scientist9, David Prieto-Merino, lecturer in medical statistics4, Abbas Dehghan, assistant professor10, Stella Trompet, senior researcher11, Andrew Wong, senior study manager12, Alana Cavadino, statistician13, Dagmar Drogan, scientist14, Sandosh Padmanabhan, reader15, Shanshan Li, postdoctoral research fellow16, Ajay Yesupriya, health scientist17, Maarten Leusink, doctoral candidate18, Johan Sundstrom, senior epidemiologist19, Jaroslav A Hubacek, senior scientist20, Hynek Pikhart, senior lecturer21, Daniel I Swerdlow, clinician scientist1, Andrie G Panayiotou, lecturer in public health22, Svetlana A Borinskaya, leading researcher23, Chris Finan, bioinformatician1, Sonia Shah, postdoctoral research fellow24, Karoline B Kuchenbaecker, research associate in genetic epidemiology25, Tina Shah, postdoctoral research fellow1, Jorgen Engmann, data manager1, Lasse Folkersen, postdoctoral research fellow26, Per Eriksson, professor of cardiovascular medicine26, Fulvio Ricceri, epidemiologist, research fellow28, Olle Melander, professor27, Carlotta Sacerdote, medical epidemiologist28, Dale M Gamble, researcher29, Sruti Rayaprolu, researcher30, Owen A Ross, associate professor30, Stela McLachlan, data manager31, Olga Vikhireva, research associate21, Ivonne Sluijs, assistant professor32, Robert A Scott, senior investigator scientist9, Vera A

History

Citation

BMJ, 2014, 349:g4164

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health Sciences

Version

VoR (Version of Record)

Published in

BMJ

Publisher

BMJ Publishing Group

eissn

1756-1833

Copyright date

2014

Available date

13/05/2019

Publisher version

https://www.bmj.com/content/349/bmj.g4164

Language

en