TY - JOUR
T1 - Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.
JF - BMJ
Y1 - 2014
A1 - Holmes, Michael V
A1 - Dale, Caroline E
A1 - Zuccolo, Luisa
A1 - Silverwood, Richard J
A1 - Guo, Yiran
A1 - Ye, Zheng
A1 - Prieto-Merino, David
A1 - Dehghan, Abbas
A1 - Trompet, Stella
A1 - Wong, Andrew
A1 - Cavadino, Alana
A1 - Drogan, Dagmar
A1 - Padmanabhan, Sandosh
A1 - Li, Shanshan
A1 - Yesupriya, Ajay
A1 - Leusink, Maarten
A1 - Sundström, Johan
A1 - Hubacek, Jaroslav A
A1 - Pikhart, Hynek
A1 - Swerdlow, Daniel I
A1 - Panayiotou, Andrie G
A1 - Borinskaya, Svetlana A
A1 - Finan, Chris
A1 - Shah, Sonia
A1 - Kuchenbaecker, Karoline B
A1 - Shah, Tina
A1 - Engmann, Jorgen
A1 - Folkersen, Lasse
A1 - Eriksson, Per
A1 - Ricceri, Fulvio
A1 - Melander, Olle
A1 - Sacerdote, Carlotta
A1 - Gamble, Dale M
A1 - Rayaprolu, Sruti
A1 - Ross, Owen A
A1 - McLachlan, Stela
A1 - Vikhireva, Olga
A1 - Sluijs, Ivonne
A1 - Scott, Robert A
A1 - Adamkova, Vera
A1 - Flicker, Leon
A1 - Bockxmeer, Frank M van
A1 - Power, Christine
A1 - Marques-Vidal, Pedro
A1 - Meade, Tom
A1 - Marmot, Michael G
A1 - Ferro, Jose M
A1 - Paulos-Pinheiro, Sofia
A1 - Humphries, Steve E
A1 - Talmud, Philippa J
A1 - Mateo Leach, Irene
A1 - Verweij, Niek
A1 - Linneberg, Allan
A1 - Skaaby, Tea
A1 - Doevendans, Pieter A
A1 - Cramer, Maarten J
A1 - van der Harst, Pim
A1 - Klungel, Olaf H
A1 - Dowling, Nicole F
A1 - Dominiczak, Anna F
A1 - Kumari, Meena
A1 - Nicolaides, Andrew N
A1 - Weikert, Cornelia
A1 - Boeing, Heiner
A1 - Ebrahim, Shah
A1 - Gaunt, Tom R
A1 - Price, Jackie F
A1 - Lannfelt, Lars
A1 - Peasey, Anne
A1 - Kubinova, Ruzena
A1 - Pajak, Andrzej
A1 - Malyutina, Sofia
A1 - Voevoda, Mikhail I
A1 - Tamosiunas, Abdonas
A1 - Maitland-van der Zee, Anke H
A1 - Norman, Paul E
A1 - Hankey, Graeme J
A1 - Bergmann, Manuela M
A1 - Hofman, Albert
A1 - Franco, Oscar H
A1 - Cooper, Jackie
A1 - Palmen, Jutta
A1 - Spiering, Wilko
A1 - de Jong, Pim A
A1 - Kuh, Diana
A1 - Hardy, Rebecca
A1 - Uitterlinden, André G
A1 - Ikram, M Arfan
A1 - Ford, Ian
A1 - Hyppönen, Elina
A1 - Almeida, Osvaldo P
A1 - Wareham, Nicholas J
A1 - Khaw, Kay-Tee
A1 - Hamsten, Anders
A1 - Husemoen, Lise Lotte N
A1 - Tjønneland, Anne
A1 - Tolstrup, Janne S
A1 - Rimm, Eric
A1 - Beulens, Joline W J
A1 - Verschuren, W M Monique
A1 - Onland-Moret, N Charlotte
A1 - Hofker, Marten H
A1 - Wannamethee, S Goya
A1 - Whincup, Peter H
A1 - Morris, Richard
A1 - Vicente, Astrid M
A1 - Watkins, Hugh
A1 - Farrall, Martin
A1 - Jukema, J Wouter
A1 - Meschia, James
A1 - Cupples, L Adrienne
A1 - Sharp, Stephen J
A1 - Fornage, Myriam
A1 - Kooperberg, Charles
A1 - LaCroix, Andrea Z
A1 - Dai, James Y
A1 - Lanktree, Matthew B
A1 - Siscovick, David S
A1 - Jorgenson, Eric
A1 - Spring, Bonnie
A1 - Coresh, Josef
A1 - Li, Yun R
A1 - Buxbaum, Sarah G
A1 - Schreiner, Pamela J
A1 - Ellison, R Curtis
A1 - Tsai, Michael Y
A1 - Patel, Sanjay R
A1 - Redline, Susan
A1 - Johnson, Andrew D
A1 - Hoogeveen, Ron C
A1 - Hakonarson, Hakon
A1 - Rotter, Jerome I
A1 - Boerwinkle, Eric
A1 - de Bakker, Paul I W
A1 - Kivimaki, Mika
A1 - Asselbergs, Folkert W
A1 - Sattar, Naveed
A1 - Lawlor, Debbie A
A1 - Whittaker, John
A1 - Davey Smith, George
A1 - Mukamal, Kenneth
A1 - Psaty, Bruce M
A1 - Wilson, James G
A1 - Lange, Leslie A
A1 - Hamidovic, Ajna
A1 - Hingorani, Aroon D
A1 - Nordestgaard, Børge G
A1 - Bobak, Martin
A1 - Leon, David A
A1 - Langenberg, Claudia
A1 - Palmer, Tom M
A1 - Reiner, Alex P
A1 - Keating, Brendan J
A1 - Dudbridge, Frank
A1 - Casas, Juan P
KW - Adult
KW - Aged
KW - Alcohol Dehydrogenase
KW - Alcohol Drinking
KW - Biomarkers
KW - Coronary Disease
KW - Female
KW - Genetic Markers
KW - Genotype
KW - Humans
KW - Male
KW - Mendelian Randomization Analysis
KW - Middle Aged
KW - Models, Statistical
KW - Polymorphism, Single Nucleotide
KW - Stroke
AB - **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.

VL - 349
U1 - http://www.ncbi.nlm.nih.gov/pubmed/25011450?dopt=Abstract
ER -