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

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.

doi:10.1136/bmj.g4164

i

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

Supporting Files

Jul 10 2014
By 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.
http://dx.doi.org/10.1136/bmj.g4164

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English

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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:
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
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