Common variants in the GDF5-UQCC region are associated with variation in human height

被引：310

作者：

Sanna, Serena ^{[2
,3
]}

Jackson, Anne U. ^{[2
]}

Nagaraja, Ramaiah ^{[4
]}

Willer, Cristen J. ^{[2
]}

Chen, Wei-Min ^{[2
,5
]}

Bonnycastle, Lori L. ^{[6
]}

Shen, Haiqing ^{[7
]}

Timpson, Nicholas ^{[8
,9
]}

Lettre, Guillaume ^{[10
]}

Usala, Gianluca ^{[3
]}

Chines, Peter S. ^{[6
]}

Stringham, Heather M. ^{[2
]}

Scott, Laura J. ^{[2
]}

Dei, Mariano ^{[3
]}

Lai, Sandra ^{[3
]}

Albai, Giuseppe ^{[3
]}

Crisponi, Laura ^{[3
]}

Naitza, Silvia ^{[3
]}

Doheny, Kimberly F. ^{[11
]}

Pugh, Elizabeth W. ^{[11
]}

Ben-Shlomo, Yoav ^{[8
]}

Ebrahim, Shah ^{[12
]}

Lawlor, Debbie A. ^{[8
,9
]}

Bergman, Richard N. ^{[13
]}

Watanabe, Richard M. ^{[13
,14
]}

Uda, Manuela ^{[3
]}

Tuomilehto, Jaakko ^{[15
,16
]}

Coresh, Josef ^{[17
]}

Hirschhorn, Joel N. ^{[10
]}

Shuldiner, Alan R. ^{[7
,18
]}

Schlessinger, David ^{[4
]}

Collins, Francis S. ^{[6
]}

Smith, George Davey ^{[8
,9
]}

Boerwinkle, Eric ^{[19
,20
]}

Cao, Antonio ^{[3
]}

Boehnke, Michael ^{[2
]}

Abecasis, Goncalo R. ^{[2
]}

Mohlke, Karen L. ^{[1
]}

机构：

[1] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[2] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[3] Citta Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy

[4] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA

[5] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA

[6] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA

[7] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[8] Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England

[9] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol BS8 2PR, Avon, England

[10] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge Ctr 7, Cambridge, MA 02142 USA

[11] Johns Hopkins Univ, Sch Med, Inst Med Genet, CIDR, Baltimore, MD 21224 USA

[12] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England

[13] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA

[14] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA

[15] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Diabet Unit, SF-00300 Helsinki, Finland

[16] Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland

[17] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA

[18] Vet Adm Med Ctr, Geriatr Res & Educ Ctr, Baltimore, MD 21201 USA

[19] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX 77225 USA

[20] Univ Texas Houston, Hlth Sci Ctr, Inst Mol Med, Houston, TX 77225 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 02期

基金：

英国医学研究理事会; 美国国家科学基金会; 英国惠康基金;

关键词：

D O I：

10.1038/ng.74

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Identifying genetic variants that influence human height will advance our understanding of skeletal growth and development. Several rare genetic variants have been convincingly and reproducibly associated with height in mendelian syndromes, and common variants in the transcription factor gene HMGA2 are associated with variation in height in the general population(1). Here we report genome-wide association analyses, using genotyped and imputed markers, of 6,669 individuals from Finland and Sardinia, and follow-up analyses in an additional 28,801 individuals. We show that common variants in the osteoarthritis-associated locus(2) GDF5-UQCC contribute to variation in height with an estimated additive effect of 0.44 cm (overall P < 10(-15)). Our results indicate that there may be a link between the genetic basis of height and osteoarthritis, potentially mediated through alterations in bone growth and development.

引用

页码：198 / 203

页数：6

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