Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone

被引：209

作者：

Albagha, Omar M. E. ^{[1
]}

Visconti, Micaela R. ^{[1
]}

Alonso, Nerea ^{[1
]}

Langston, Anne L. ^{[1
,2
]}

Cundy, Tim ^{[3
]}

Dargie, Rosemary ^{[4
]}

Dunlop, Malcolm G. ^{[5
]}

Fraser, William D. ^{[6
]}

Hooper, Michael J. ^{[7
,8
]}

Isaia, Gianluca ^{[9
]}

Nicholson, Geoff C. ^{[10
]}

del Pino Montes, Javier ^{[11
,12
]}

Gonzalez-Sarmiento, Rogelio ^{[11
,12
]}

di Stefano, Marco ^{[9
]}

Tenesa, Albert ^{[5
]}

Walsh, John P. ^{[13
]}

Ralston, Stuart H. ^{[1
,2
]}

机构：

[1] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Rheumat Dis Unit, Edinburgh, Midlothian, Scotland

[2] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Edinburgh Clin Trials Unit, Edinburgh, Midlothian, Scotland

[3] Univ Auckland, Dept Med, Auckland, New Zealand

[4] Glasgow Royal Infirm, Univ Dept Med, Glasgow G4 0SF, Lanark, Scotland

[5] Univ Edinburgh, Human Genet Unit, MRC, Western Gen Hosp,Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland

[6] Royal Liverpool Univ Hosp, Dept Clin Chem, Liverpool, Merseyside, England

[7] Univ Sydney, Dept Med, Sydney, NSW 2006, Australia

[8] Cent Sydney Area Hlth Serv, Sydney, NSW, Australia

[9] Univ Turin, Dept Med & Surg, Geriatr Sect, Turin, Italy

[10] Univ Melbourne, Geelong Hosp, Dept Clin & Biomed Sci, Melbourne, Vic, Australia

[11] Univ Salamanca, Dept Med, Unidad Med Mol, E-37008 Salamanca, Spain

[12] Hosp Univ Salamanca, RETICEF, Salamanca, Spain

[13] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA, Australia

来源：

NATURE GENETICS | 2010年 / 42卷 / 06期

基金：

英国医学研究理事会;

关键词：

COLONY-STIMULATING FACTOR; FAMILIAL EXPANSILE OSTEOLYSIS; NF-KAPPA-B; SUSCEPTIBILITY LOCI; MINERAL DENSITY; OPTINEURIN; RANK; OSTEOCLASTOGENESIS; MUTATIONS; DUPLICATION;

D O I：

10.1038/ng.562

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Paget's disease of bone (PDB) is a common disorder with a strong genetic component characterized by focal increases in bone turnover, which in some cases is caused by mutations in SQSTM1. To identify additional susceptibility genes, we performed a genome-wide association study in 750 individuals with PDB (cases) without SQSTM1 mutations and 1,002 controls and identified three candidate disease loci, which were then replicated in an independent set of 500 cases and 535 controls. The strongest signal was with rs484959 on 1p13 near the CSF1 gene (P = 5.38 x 10(-24)). Significant associations were also observed with rs1561570 on 10p13 within the OPTN gene (P = 6.09 x 10(-13)) and with rs3018362 on 18q21 near the TNFRSF11A gene (P = 5.27 x 10(-13)). These studies provide new insights into the pathogenesis of PDB and identify OPTN, CSF1 and TNFRSF11A as candidate genes for disease susceptibility.

引用

页码：520 / U26

页数：6

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