Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.
BMJ (Clinical research ed.) 2014 ; 349: g4164.
Holmes MV, Dale CE, Zuccolo L, Silverwood RJ, Guo Y, Ye Z, Prieto-Merino D, Dehghan A, Trompet S, Wong A, Cavadino A, Drogan D, Padmanabhan S, Li S, Yesupriya A, Leusink M, Sundström J, Hubacek JA, Pikhart H, Swerdlow DI, Panayiotou AG, Borinskaya SA, Finan C, Shah S, Kuchenbaecker KB, Shah T, Engmann J, Folkersen L, Eriksson P, Ricceri F, Melander O, Sacerdote C, Gamble DM, Rayaprolu S, Ross OA, McLachlan S, Vikhireva O, Sluijs I, Scott RA, Adamkova V, Flicker L, Bockxmeer FM, Power C, Marques-Vidal P, Meade T, Marmot MG, Ferro JM, Paulos-Pinheiro S, Humphries SE, Talmud PJ, Mateo Leach I, Verweij N, Linneberg A, Skaaby T, Doevendans PA, Cramer MJ, van der Harst P, Klungel OH, Dowling NF, Dominiczak AF, Kumari M, Nicolaides AN, Weikert C, Boeing H, Ebrahim S, Gaunt TR, Price JF, Lannfelt L, Peasey A, Kubinova R, Pajak A, Malyutina S, Voevoda MI, Tamosiunas A, Maitland-van der Zee AH, Norman PE, Hankey GJ, Bergmann MM, Hofman A, Franco OH, Cooper J, Palmen J, Spiering W, de Jong PA, Kuh D, Hardy R, Uitterlinden AG, Ikram MA, Ford I, Hyppönen E, Almeida OP, Wareham NJ, Khaw KT, Hamsten A, Husemoen LL, Tjønneland A, Tolstrup JS, Rimm E, Beulens JW, Verschuren WM, Onland-Moret NC, Hofker MH, Wannamethee SG, Whincup PH, Morris R, Vicente AM, Watkins H, Farrall M, Jukema JW, Meschia J, Cupples LA, Sharp SJ, Fornage M, Kooperberg C, Lacroix AZ, Dai JY, Lanktree MB, Siscovick DS, Jorgenson E, Spring B, Coresh J, Li YR, Buxbaum SG, Schreiner PJ, Ellison RC, Tsai MY, Patel SR, Redline S, Johnson AD, Hoogeveen RC, Hakonarson H, Rotter JI, Boerwinkle E, de Bakker PI, Kivimaki M, Asselbergs FW, Sattar N, Lawlor DA, Whittaker J, Davey Smith G, Mukamal K, Psaty BM, Wilson JG, Lange LA, Hamidovic A, Hingorani AD, Nordestgaard BG, Bobak M, Leon DA, Langenberg C, Palmer TM, Reiner AP, Keating BJ, Dudbridge F, Casas JP, and InterAct Consortium
DOI : 10.1136/bmj.g4164
PubMed ID : 25011450
PMCID : PMC4091648
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.
Mendelian randomisation meta-analysis of 56 epidemiological studies.
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.
Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption.
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)).
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.