Holmes, Michael V3; Dale, Caroline E3; Zuccolo, Luisa3; Silverwood, Richard J3; Guo, Yiran3; Ye, Zheng3; Prieto-Merino, David3; Dehghan, Abbas3; Trompet, Stella3; Wong, Andrew3; Cavadino, Alana3; Drogan, Dagmar3; Padmanabhan, Sandosh3; Li, Shanshan3; Yesupriya, Ajay3; Leusink, Maarten3; Sundstrom, Johan3; Hubacek, Jaroslav A3; Pikhart, Hynek3; Swerdlow, Daniel I3; Panayiotou, Andrie G3; Borinskaya, Svetlana A3; Finan, Chris3; Shah, Sonia3; Kuchenbaecker, Karoline B3; Shah, Tina3; Engmann, Jorgen3; Folkersen, Lasse3; Eriksson, Per3; Ricceri, Fulvio3; Melander, Olle3; Sacerdote, Carlotta3; Gamble, Dale M3; Rayaprolu, Sruti3; Ross, Owen A3; McLachlan, Stela3; Vikhireva, Olga3; Sluijs, Ivonne3; Scott, Robert A3; Adamkova, Vera3; Flicker, Leon3; Bockxmeer, Frank M van3; Power, Christine3; Marques-Vidal, Pedro3; Meade, Tom3; Marmot, Michael G3; Ferro, Jose M3; Paulos-Pinheiro, Sofia3; Humphries, Steve E3; Talmud, Philippa J3; Mateo Leach, Irene3; Verweij, Niek3; Linneberg, Allan4; Skaaby, Tea3; Doevendans, Pieter A3; Cramer, Maarten J3; van der Harst, Pim3; Klungel, Olaf H3; Dowling, Nicole F3; Dominiczak, Anna F3; Kumari, Meena3; Nicolaides, Andrew N3; Weikert, Cornelia3; Boeing, Heiner3; Ebrahim, Shah3; Gaunt, Tom R3; Price, Jackie F3; Lannfelt, Lars3; Peasey, Anne3; Kubinova, Ruzena3; Pajak, Andrzej3; Malyutina, Sofia3; Voevoda, Mikhail I3; Tamosiunas, Abdonas3; Maitland-van der Zee, Anke H3; Norman, Paul E3; Hankey, Graeme J3; Bergmann, Manuela M3; Hofman, Albert3; Franco, Oscar H3; Cooper, Jackie3; Palmen, Jutta3; Spiering, Wilko3; de Jong, Pim A3; Kuh, Diana3; Hardy, Rebecca3; Uitterlinden, Andre G3; Ikram, M Arfan3; Ford, Ian3; Hyppönen, Elina3; Almeida, Osvaldo P3; Wareham, Nicholas J3; Khaw, Kay-Tee3; Hamsten, Anders3; Husemoen, Lise Lotte N3; Tjønneland, Anne3; Tolstrup, Janne S3; Rimm, Eric3; Beulens, Joline W J3; Verschuren, W M Monique3; Onland-Moret, N Charlotte3; Hofker, Marten H3; Wannamethee, S Goya3; Whincup, Peter H3; Morris, Richard3; Vicente, Astrid M3; Watkins, Hugh3; Farrall, Martin3; Jukema, J Wouter3; Meschia, James3; Cupples, L Adrienne3; Sharp, Stephen J3; Fornage, Myriam3; Kooperberg, Charles3; LaCroix, Andrea Z3; Dai, James Y3; Lanktree, Matthew B3; Siscovick, David S3; Jorgenson, Eric3; Spring, Bonnie3; Coresh, Josef3; Li, Yun R3; Buxbaum, Sarah G3; Schreiner, Pamela J3; Ellison, R Curtis3; Tsai, Michael Y3; Patel, Sanjay R3; Redline, Susan3; Johnson, Andrew D3; Hoogeveen, Ron C3; Hakonarson, Hakon3; Rotter, Jerome I3; Boerwinkle, Eric3; de Bakker, Paul I W3; Kivimaki, Mika3; Asselbergs, Folkert W3; Sattar, Naveed3; Lawlor, Debbie A3; Whittaker, John3; Davey Smith, George3; Mukamal, Kenneth3; Psaty, Bruce M3; Wilson, James G3; Lange, Leslie A3; Hamidovic, Ajna3; Hingorani, Aroon D3; Nordestgaard, Børge G4; Bobak, Martin3; Leon, David A3; Langenberg, Claudia3; Palmer, Tom M3; Reiner, Alex P3; Keating, Brendan J3; Dudbridge, Frank3; Casas, Juan P3
1 Medicinsk Sociologi, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Mendelian randomisation analysis based on individual participant data
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.