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

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• Alternative Title:
  BMJ
• Personal Author:
  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. ; van der Harst, Pim ; 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 ; de Jong, Pim A. ; 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.
• Description:
  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.
• Subjects:
  Adult Aged Alcohol Dehydrogenase Alcohol Drinking Biological Markers Coronary Disease Female Genetic Markers Genotype Humans Male Mendelian Randomization Analysis Middle Aged Models, Statistical Polymorphism, Single Nucleotide Stroke

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• Source:
  BMJ. 2014; 349.
• Document Type:
  Journal Article
• Funding:
  0090049/Department of Health/United Kingdom ; 064947/Z/01/Z/Wellcome Trust/United Kingdom ; 076113/Wellcome Trust/United Kingdom ; 078557/Wellcome Trust/United Kingdom ; 081081/Z/06/Z/Wellcome Trust/United Kingdom ; 090532/Z/09/Z/Wellcome Trust/United Kingdom ; 092731/Wellcome Trust/United Kingdom ; 1R01 AG23522/AG/NIA NIH HHS/United States ; AA021223-01/AA/NIAAA NIH HHS/United States ; AA11181/AA/NIAAA NIH HHS/United States ; AG023629/AG/NIA NIH HHS/United States ; AG13196/AG/NIA NIH HHS/United States ; AG1764406S1/AG/NIA NIH HHS/United States ; CA55075/CA/NCI NIH HHS/United States ; CA87969/CA/NCI NIH HHS/United States ; CH/98001/British Heart Foundation/United Kingdom ; F32DA024920/DA/NIDA NIH HHS/United States ; G0000934/Medical Research Council/United Kingdom ; G0701863/Medical Research Council/United Kingdom ; G0802432/Medical Research Council/United Kingdom ; G0902144/Medical Research Council/United Kingdom ; G1000143/Medical Research Council/United Kingdom ; G1000718/Medical Research Council/United Kingdom ; HHSN268200625226C/PHS HHS/United States ; HHSN268200800007C/PHS HHS/United States ; HHSN268200900009C/PHS HHS/United States ; HHSN268200960009C/PHS HHS/United States ; HHSN268201100001C/PHS HHS/United States ; HHSN268201100002C/PHS HHS/United States ; HHSN268201100003C/PHS HHS/United States ; HHSN268201100004C/PHS HHS/United States ; HHSN268201100005C/PHS HHS/United States ; HHSN268201100006C/PHS HHS/United States ; HHSN268201100007C/PHS HHS/United States ; HHSN268201100008C/PHS HHS/United States ; HHSN268201100009C/PHS HHS/United States ; HHSN268201100010C/PHS HHS/United States ; HHSN268201100011C/PHS HHS/United States ; HHSN268201100012C/PHS HHS/United States ; HHSN268201100046C/PHS HHS/United States ; HHSN268201200036C/PHS HHS/United States ; HHSN271201100004C/PHS HHS/United States ; HL 114901/HL/NHLBI NIH HHS/United States ; HL080295/HL/NHLBI NIH HHS/United States ; HL34594/HL/NHLBI NIH HHS/United States ; HL35464/HL/NHLBI NIH HHS/United States ; HL36310/HL/NHLBI NIH HHS/United States ; HL46380/HL/NHLBI NIH HHS/United States ; MC_U106179471/Medical Research Council/United Kingdom ; MC_UU_12013/1/Medical Research Council/United Kingdom ; MC_UU_12013/8/Medical Research Council/United Kingdom ; MC_UU_12015/1/Medical Research Council/United Kingdom ; MC_UU_12019/1/Medical Research Council/United Kingdom ; MR/K013351/1/Medical Research Council/United Kingdom ; MRC G0601653/Medical Research Council/United Kingdom ; N01 HC55222/HC/NHLBI NIH HHS/United States ; N01-HC-48047/HC/NHLBI NIH HHS/United States ; N01-HC-48048/HC/NHLBI NIH HHS/United States ; N01-HC-48049/HC/NHLBI NIH HHS/United States ; N01-HC-48050/HC/NHLBI NIH HHS/United States ; N01-HC-95095/HC/NHLBI NIH HHS/United States ; N01HC65226/HC/NHLBI NIH HHS/United States ; N01HC85079/HC/NHLBI NIH HHS/United States ; N01HC85080/HC/NHLBI NIH HHS/United States ; N01HC85081/HC/NHLBI NIH HHS/United States ; N01HC85082/HC/NHLBI NIH HHS/United States ; N01HC85083/HC/NHLBI NIH HHS/United States ; N01HC85086/HC/NHLBI NIH HHS/United States ; NF-SI-0512-10114/Department of Health/United Kingdom ; NF-SI-0512-10135/Department of Health/United Kingdom ; NHLBI 33014/PHS HHS/United States ; NIH HL075451/HL/NHLBI NIH HHS/United States ; P20MD006899/MD/NIMHD NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; PG/07/131/24254/British Heart Foundation/United Kingdom ; PG/09/022/British Heart Foundation/United Kingdom ; PG/13/66/30442/British Heart Foundation/United Kingdom ; PG/2008/008/British Heart Foundation/United Kingdom ; R01 42733/PHS HHS/United States ; R01 NS39987/NS/NINDS NIH HHS/United States ; R01HL086694/HL/NHLBI NIH HHS/United States ; R01HL087641/HL/NHLBI NIH HHS/United States ; R01HL59367/HL/NHLBI NIH HHS/United States ; RG/07/005/23633/British Heart Foundation/United Kingdom ; RG/08/013/25942/British Heart Foundation/United Kingdom ; RG/10/12/28456/British Heart Foundation/United Kingdom ; RG/98002/British Heart Foundation/United Kingdom ; RG2008/014/British Heart Foundation/United Kingdom ; U01 DK062418/DK/NIDDK NIH HHS/United States ; U01HG004402/HG/NHGRI NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; UL1RR025005/RR/NCRR NIH HHS/United States ; WT087997MA/Wellcome Trust/United Kingdom ; WT088806/Wellcome Trust/United Kingdom
• Volume:
  349
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:04d5ed163316789849fd80ad40a12ef9e196dfb3c566a0ed5a3974f60942ac0e
• Download URL:
  https://stacks.cdc.gov/view/cdc/26778/cdc_26778_DS1.pdf
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  [PDF - 2.80 MB ]