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

Holmes, MV and Dale, CE and Zuccolo, L and Silverwood, RJ and Guo, Y and Ye, Z and Prieto-Merino, D and Dehghan, A and Trompet, S and Wong, A and Cavadino, A and Drogan, D and Padmanabhan, S and Li, S and Yesupriya, A and Leusink, M and Sundstrom, J and Hubacek, JA and Pikhart, H and Swerdlow, DI and Panayiotou, AG and Borinskaya, SA and Finan, C and Shah, S and Kuchenbaecker, KB and Shah, T and Engmann, J and Folkersen, L and Eriksson, P and Ricceri, F and Melander, O and Sacerdote, C and Gamble, DM and Rayaprolu, S and Ross, OA and McLachlan, S and Vikhireva, O and Sluijs, I and Scott, RA and Adamkova, V and Flicker, L and Bockxmeer, FMV and Power, C and Marques-Vidal, P and Meade, T and Marmot, MG and Ferro, JM and Paulos-Pinheiro, S and Humphries, SE and Talmud, PJ and Leach, IM and Verweij, N and Linneberg, A and Skaaby, T and Doevendans, PA and Cramer, MJ and Harst, PVD and Klungel, OH and Dowling, NF and Dominiczak, AF and Kumari, M and Nicolaides, AN and Weikert, C and Boeing, H and Ebrahim, S and Gaunt, TR and Price, JF and Lannfelt, L and Peasey, A and Kubinova, R and Pajak, A and Malyutina, S and Voevoda, MI and Tamosiunas, A and Maitland-van der Zee, AH and Norman, PE and Hankey, GJ and Bergmann, MM and Hofman, A and Franco, OH and Cooper, J and Palmen, J and Spiering, W and Jong, PAD and Kuh, D and Hardy, R and Uitterlinden, AG and Ikram, MA and Ford, I and Hypponen, E and Almeida, OP and Wareham, NJ and Khaw, K-T and Hamsten, A and Husemoen, LLN and Tjonneland, A and Tolstrup, JS and Rimm, E and Beulens, JWJ and Verschuren, WMM and Onland-Moret, NC and Hofker, MH and Wannamethee, SG and Whincup, PH and Morris, R and Vicente, AM and Watkins, H and Farrall, M and Jukema, JW and Meschia, J and Cupples, LA and Sharp, SJ and Fornage, M and Kooperberg, C and LaCroix, AZ and Dai, JY and Lanktree, MB and Siscovick, DS and Jorgenson, E and Spring, B and Coresh, J and Li, YR and Buxbaum, SG and Schreiner, PJ and Ellison, RC and Tsai, MY and Patel, SR and Redline, S and Johnson, AD and Hoogeveen, RC and Hakonarson, H and Rotter, JI and Boerwinkle, E and Bakker, PIWD and Kivimaki, M and Asselbergs, FW and Sattar, N and Lawlor, DA and Whittaker, J and Davey Smith, G and Mukamal, K and Psaty, BM and Wilson, JG and Lange, LA and Hamidovic, A and Hingorani, AD and Nordestgaard, BG and Bobak, M and Leon, DA and Langenberg, C and Palmer, TM and Reiner, AP and Keating, BJ and Dudbridge, F and Casas, JP (2014) 'Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.' BMJ, 349 (jul10 ). g4164-g4164. ISSN 1756-1833

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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.

Item Type: Article
Uncontrolled Keywords: InterAct Consortium; Humans; Coronary Disease; Alcohol Dehydrogenase; Genetic Markers; Models, Statistical; Alcohol Drinking; Genotype; Polymorphism, Single Nucleotide; Adult; Aged; Middle Aged; Female; Male; Stroke; Mendelian Randomization Analysis; Biomarkers
Subjects: H Social Sciences > H Social Sciences (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences
Faculty of Social Sciences > Institute for Social and Economic Research
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 10 Feb 2015 14:24
Last Modified: 15 Jan 2022 00:42
URI: http://repository.essex.ac.uk/id/eprint/12691

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