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Journal Article

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

Authors

Publication date

2014

Summary

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.

Published in

BMJ

Volume

349

DOI

http://dx.doi.org/10.1136/bmj.g4164

ISSN

16

Subjects

Drug/Alcohol Abuse, Medicine, Health, and Biology

Notes

Open Access article; Full author list: 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.; Harst, Pim van der; 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; Jong, Pim A. de; 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.; Rimm, Eric; 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.; Patel, Sanjay R.; Redline, Susan; 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; Mukamal, Kenneth; 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.

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