Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis

被引：89

作者：

Nuesch, Eveline ^{[1
,2
,3
]}

Dale, Caroline ^{[1
]}

Palmer, Tom M. ^{[4
,5
]}

White, Jon ^{[6
]}

Keating, Brendan J. ^{[7
,8
,9
]}

van Iperen, Erik P. A. ^{[10
,15
]}

Goel, Anuj ^{[11
,12
]}

Padmanabhan, Sandosh ^{[13
]}

WAsselbergs, Folkert ^{[14
,15
,16
]}

Lange, Leslie A. ^{[18
]}

Hovingh, G. K. ^{[19
]}

Sivapalaratnam, Suthesh ^{[19
]}

Morris, Richard W. ^{[20
]}

Whincup, Peter H. ^{[21
]}

Wannamethe, Goya S. ^{[20
]}

Gaunt, Tom R. ^{[22
,23
]}

Ebrahim, Shah ^{[1
]}

Steel, Laura ^{[7
]}

Nair, Nikhil ^{[7
]}

Reiner, Alexander P. ^{[24
,25
]}

Kooperberg, Charles ^{[25
]}

Wilson, James F. ^{[26
,27
]}

Bolton, Jennifer L. ^{[26
]}

McLachlan, Stela ^{[26
]}

Price, Jacqueline F. ^{[26
]}

Strachan, Mark W. J. ^{[28
]}

Robertson, Christine M. ^{[26
]}

Kleber, Marcus E. ^{[29
]}

Delgado, Graciela ^{[29
]}

Marz, Winfried ^{[30
,31
,32
,33
]}

Melander, Olle ^{[34
]}

Dominiczak, Anna F. ^{[13
]}

Farrall, Martin ^{[11
,12
]}

Watkins, Hugh ^{[11
,12
]}

Leusink, Maarten ^{[35
,36
]}

Maitland-van der Zee, Anke H. ^{[35
]}

de Groot, Mark C. H. ^{[35
,36
]}

Dudbridge, Frank ^{[1
]}

Hingorani, Aroon ^{[37
]}

Ben-Shlomo, Yoav ^{[23
]}

Lawlor, Debbie A. ^{[22
,23
]}

Smith, George Davey ^{[22
,23
]}

Wells, Jonathan C. ^{[39
]}

Leon, David A. ^{[1
,40
]}

Holmes, Michael V. ^{[16
,41
,42
,43
,44
]}

Casas, Juan P. ^{[1
,16
]}

机构：

[1] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London, England

[2] Univ Bern, CTU Bern, Dept Clin Res, Bern, Switzerland

[3] Univ Bern, ISPM, Bern, Switzerland

[4] Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England

[5] Univ Lancaster, Dept Math & Stat, Lancaster, England

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

[7] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA

[8] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA

[9] Univ Penn, Div Genet, Philadelphia, PA 19104 USA

[10] Acad Med Ctr Amsterdam, Dept Biostat, Amsterdam, Netherlands

[11] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[12] Univ Oxford, Radcliffe Dept Med, Oxford, England

[13] Univ Glasgow, Inst Cardiovasc & Med Sci, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland

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

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

[16] UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England

[17] EPIC NL, Utrecht, Netherlands

[18] Univ North Carolina Chapel Hill, Dept Genet, Chapel Hill, NC USA

[19] Acad Med Ctr Amsterdam, Dept Vasc Med, Amsterdam, Netherlands

[20] UCL, Dept Primary Care & Populat Hlth, London, England

[21] St Georges Univ London, Populat Hlth Res Inst, London, England

[22] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England

[23] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England

[24] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[25] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

[26] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland

[27] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[28] Western Gen Hosp, Metab Unit, Edinburgh, Midlothian, Scotland

[29] Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany

[30] Heidelberg Univ, Med Clin Nephrol Hypertensiol Endocrinol Diabetol, Mannheim Med Fac, Heidelberg, Germany

[31] Synlab Serv GmbH, Synlab Acad, Mannheim, Germany

[32] Synlab Serv GmbH, Synlab Acad, Augsburg, Germany

[33] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria

[34] Lund Univ, Lund, Sweden

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

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

[37] UCL, Sch Med, Dept Epidemiol & Publ Hlth, London, England

[38] UCLEB, Bristol, Avon, England

[39] UCL Inst Child Hlth, Childhood Nutr Res Ctr, London, England

[40] Arctic Univ Norway, UiT, Dept Community Med, Tromso, Norway

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

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

[43] Univ Oxford, Clin Trial Serv Unit, Nuffield Dept Populat Hlth, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England

[44] Univ Oxford, Epidemiol Studies Unit CTSU, Nuffield Dept Populat Hlth, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England

来源：

INTERNATIONAL JOURNAL OF EPIDEMIOLOGY | 2016年 / 45卷 / 06期

基金：

英国医学研究理事会; 美国国家卫生研究院; 英国惠康基金;

关键词：

MULTIPLE GENETIC-VARIANTS; INSTRUMENTAL VARIABLES; OBESITY; RISK; MORTALITY; WEIGHT; DESIGN; LONDON; WOMEN;

D O I：

10.1093/ije/dyv074

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

Background: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. Methods: We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D. Results: IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively], which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index (P<0.001), triglycerides (P<0.001), non high-density (non-HDL) cholesterol (P<0.001), C-reactive protein (P = 0.042), and systolic blood pressure (P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity (P<0.001 for both). Conclusions: Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure.

引用

页码：1927 / 1937

页数：11

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