Genome-wide association analysis identifies 20 loci that influence adult height

被引：630

作者：

Weedon, Michael N. ^{[1
,2
]}

Lango, Hana ^{[1
,2
]}

Lindgren, Cecilia M. ^{[3
,4
]}

Wallace, Chris ^{[5
]}

Evans, David M. ^{[6
]}

Mangino, Massimo ^{[7
]}

Freathy, Rachel M. ^{[1
,2
]}

Perry, John R. B. ^{[1
,2
]}

Stevens, Suzanne ^{[7
]}

Hall, Alistair S. ^{[8
]}

Samani, Nilesh J. ^{[7
]}

Shields, Beverly ^{[2
]}

Prokopenko, Inga ^{[3
,4
]}

Farrall, Martin ^{[9
]}

Dominiczak, Anna ^{[10
]}

Johnson, Toby ^{[11
,13
]}

Bergmann, Sven ^{[11
,12
]}

Beckmann, Jacques S. ^{[11
,14
]}

Vollenweider, Peter ^{[15
]}

Waterworth, Dawn M. ^{[16
]}

Mooser, Vincent ^{[16
]}

Palmer, Colin N. A. ^{[17
]}

Morris, Andrew D. ^{[18
]}

Ouwehand, Willem H. ^{[19
,20
]}

Caulfield, Mark

Munroe, Patricia B. ^{[5
]}

Hattersley, Andrew T. ^{[1
,2
]}

McCarthy, Mark I. ^{[3
,4
]}

Frayling, Timothy M. ^{[1
,2
]}

机构：

[1] Penn Med Sch, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England

[2] Penn Med Sch, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England

[3] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[4] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Med, Oxford OX3 7LJ, England

[5] Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol & Barts & London Genome Ctr, London EC1M 6BQ, England

[6] Univ Bristol, Dept Social Med, MRC, Ctr Causal Anal Translat Epidemiol, Bristol BS8 2PR, Avon, England

[7] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England

[8] Univ Leeds, Fac Med & Hlth, Leeds Inst Genet Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England

[9] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[10] Univ Glasgow, British Heart Fdn Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland

[11] Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland

[12] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[13] CHU Vaudois, Inst Univ Med Sociale & Prevent, CH-1011 Lausanne, Switzerland

[14] CHU Vaudois, Serv Med Genet, CH-1011 Lausanne, Switzerland

[15] CHU Vaudois, Dept Med, CH-1011 Lausanne, Switzerland

[16] GlaxoSmithKline Inc, Med Genet Clin Pharmacol & Discovery Med, King Of Prussia, PA 19406 USA

[17] Univ Dundee, Ninewells Hosp & Med Sch, Populat Pharmacogenet Grp, Biomed Res Ctr, Dundee DD1 9SY, Scotland

[18] Univ Dundee, Ninewells Hosp & Med Sch, Diabet Res Grp, Div Med & Therapeut, Dundee DD1 9SY, Scotland

[19] Univ Cambridge, Dept Haematol, Cambridge CB2 2BT, England

[20] Cambridge Ctr, Natl Hlth Serv Blood & Transplant, Cambridge CB2 2BT, England

来源：

NATURE GENETICS | 2008年 / 40卷 / 05期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1038/ng.121

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height ( P < 5 x 10(-7), with 10 reaching P < 1 iota x 10(-10)). Combined, the 20 SNPs explain similar to 3% of height variation, with a similar to 5 cm difference between the 6.2% of people with iota 7 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling ( IHH, HHIP, PTCH1), extracellular matrix ( EFEMP1, ADAMTSL3, ACAN) and cancer ( CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.

引用

页码：575 / 583

页数：9

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