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

被引：482

作者：

Holmes, Michael V. ^{[1
,2
,3
]}

Dale, Caroline E. ^{[4
]}

Zuccolo, Luisa ^{[5
]}

Silverwood, Richard J. ^{[4
,6
]}

Guo, Yiran ^{[7
,8
]}

Ye, Zheng ^{[9
]}

Prieto-Merino, David ^{[4
]}

Dehghan, Abbas ^{[10
]}

Trompet, Stella ^{[11
]}

Wong, Andrew ^{[12
]}

Cavadino, Alana ^{[13
]}

Drogan, Dagmar ^{[14
]}

Padmanabhan, Sandosh ^{[15
]}

Li, Shanshan ^{[16
]}

Yesupriya, Ajay ^{[17
]}

Leusink, Maarten ^{[18
]}

Sundstrom, Johan ^{[19
]}

Hubacek, Jaroslav A. ^{[20
]}

Pikhart, Hynek ^{[21
]}

Swerdlow, Daniel I. ^{[1
]}

Panayiotou, Andrie G. ^{[22
]}

Borinskaya, Svetlana A. ^{[23
]}

Finan, Chris ^{[1
]}

Shah, Sonia ^{[24
]}

Kuchenbaecker, Karoline B. ^{[25
]}

Shah, Tina ^{[1
]}

Engmann, Jorgen ^{[1
]}

Folkersen, Lasse ^{[26
]}

Eriksson, Per ^{[26
]}

Ricceri, Fulvio ^{[28
,29
]}

Melander, Olle ^{[27
]}

Sacerdote, Carlotta ^{[28
,29
]}

Gamble, Dale M. ^{[30
]}

Rayaprolu, Sruti ^{[31
]}

Ross, Owen A. ^{[31
]}

McLachlan, Stela ^{[32
]}

Vikhireva, Olga ^{[21
]}

Sluijs, Ivonne ^{[33
]}

Scott, Robert A. ^{[9
]}

Adamkova, Vera ^{[34
]}

Flicker, Leon ^{[35
]}

Van Bockxmeer, Frank M. ^{[36
,37
]}

Power, Christine ^{[13
]}

Marques-Vidal, Pedro ^{[38
]}

Meade, Tom ^{[4
]}

Marmot, Michael G. ^{[39
]}

Ferro, Jose M. ^{[40
,41
]}

Paulos-Pinheiro, Sofia ^{[42
,43
]}

Humphries, Steve E.

Talmud, Philippa J. ^{[44
]}

机构：

[1] UCL, Dept Epidemiol & Publ Hlth, Inst Cardiovasc Sci, Genet Epidemiol Grp, London WC1E 6BT, England

[2] Univ Penn, Perelman Sch Med, Penn Transplant Inst, Dept Surg, Philadelphia, PA 19104 USA

[3] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA

[4] Univ London, Fac Epidemiol & Publ Hlth, London Sch Hyg & Trop Med, Keppel St, London WC1E 7HT, England

[5] Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol BS8 2BN, Avon, England

[6] Univ London, Ctr Stat Methodol, London Sch Hyg & Trop Med, London WC1E 7HT, England

[7] Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA

[8] BGI Shenzhen, Shenzhen 518083, Peoples R China

[9] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England

[10] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[11] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RA Leiden, Netherlands

[12] UCL, MRC Unit Lifelong Hlth & Ageing, London, England

[13] UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England

[14] German Inst Human Nutr Potsdam Rehbrucke, D-14558 Nuthetal, Germany

[15] Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland

[16] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[17] Ctr Dis Control & Prevent, Off Epidemiol Surveillance & Lab Serv, Off Publ Hlth Genom, Atlanta, GA 30333 USA

[18] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands

[19] Uppsala Univ, Univ Uppsala Hosp, Dept Med Sci, SE-75185 Uppsala, Sweden

[20] Inst Clin & Expt Med, Ctr Med Expt, Prague 14021 4, Czech Republic

[21] UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England

[22] Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth Assoc Harvar, CY-3603 Limassol, Cyprus

[23] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow, Russia

[24] UCL Genet Inst, Dept Genet Environm & Evolut, London WC1E 6BT, England

[25] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England

[26] Karolinska Inst, Dept Med, Ctr Mol Med, Atherosclerosis Res Unit, Stockholm, Sweden

[27] Lund Univ, Dept Clin Sci, Malmo, Sweden

[28] San Giovanni Battista Hosp, Unit Canc Epidemiol, I-10129 Turin, Italy

[29] Ctr Canc Prevent CPO Piemonte, I-10129 Turin, Italy

[30] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[31] Mayo Clin Florida, Dept Neurosci, Jacksonville, FL USA

[32] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland

[33] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[34] Inst Clin & Expt Med, Dept Prevent Cardiol, Prague 14021 4, Czech Republic

[35] Univ Western Australia, Med Res Ctr, Western Australian Ctr Hlth & Ageing, Perth, WA 6009, Australia

[36] Royal Perth Hosp, Dept Clin Biochem, Perth, WA, Australia

[37] Univ Western Australia, Sch Surg, Nedlands, WA 6009, Australia

[38] CHU Vaudois, Dept Internal Med, Lausanne, Switzerland

[39] UCL Inst Hlth Equ, Dept Epidemiol & Publ Hlth, London WC1E 7HB, England

[40] Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal

[41] Hosp Santa Maria, Serv Neurol, P-1649035 Lisbon, Portugal

[42] Inst Nacl Saude Doutor Ricardo Jorge, P-1649016 Lisbon, Portugal

[43] Univ Lisbon, Fac Ciencias, P-1749016 Lisbon, Portugal

[44] UCL, Inst Cardiovasc Sci, Ctr Cardiovascular Genet, London, England

[45] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9713 AV Groningen, Netherlands

[46] Glostrup Univ Hosp, Capital Region Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark

[47] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands

[48] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands

[49] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands

[50] Ayios Dometios, Vasc Screening & Diagnost Ctr, Nicosia, Cyprus

来源：

BMJ-BRITISH MEDICAL JOURNAL | 2014年 / 349卷

基金：

美国国家卫生研究院; 英国惠康基金; 英国医学研究理事会; 芬兰科学院; 英国经济与社会研究理事会; 瑞典研究理事会;

关键词：

CORONARY-HEART-DISEASE; RISK-FACTORS; CONSUMPTION; HEALTH; DEHYDROGENASE; DEPENDENCE; MORTALITY; DESIGN; BURDEN; COHORT;

D O I：

10.1136/bmj.g4164

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.

引用

页数：16

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