Genome-wide association identifies three new susceptibility loci for Paget's disease of bone

被引：119

作者：

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

Wani, Sachin E. ^{[1
]}

Visconti, Micaela R. ^{[1
]}

Alonso, Nerea ^{[1
]}

Goodman, Kirsteen ^{[2
]}

Brandi, Maria Luisa ^{[3
]}

Cundy, Tim ^{[4
]}

Chung, Pui Yan Jenny ^{[5
]}

Dargie, Rosemary ^{[6
]}

Devogelaer, Jean-Pierre ^{[7
]}

Falchetti, Alberto ^{[3
]}

Fraser, William D. ^{[8
]}

Gennari, Luigi ^{[9
]}

Gianfrancesco, Fernando ^{[10
]}

Hooper, Michael J. ^{[11
]}

Van Hul, Wim ^{[5
]}

Isaia, Gianluca ^{[12
]}

Nicholson, Geoff C. ^{[13
]}

Nuti, Ranuccio ^{[9
]}

Papapoulos, Socrates ^{[14
]}

del Pino Montes, Javier ^{[15
]}

Ratajczak, Thomas ^{[16
,17
]}

Rea, Sarah L. ^{[16
,17
]}

Rendina, Domenico ^{[18
]}

Gonzalez-Sarmiento, Rogelio ^{[19
]}

Di Stefano, Marco ^{[12
]}

Ward, Lynley C. ^{[16
]}

Walsh, John P. ^{[16
,20
]}

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, Edinburgh Clin Trials Unit, Edinburgh, Midlothian, Scotland

[3] Univ Florence, Dept Internal Med, Florence, Italy

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

[5] Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium

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

[7] Catholic Univ Louvain, St Luc Univ Hosp, Dept Rheumatol, Brussels, Belgium

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

[9] Univ Siena, Dept Internal Med Endocrine Metab Sci & Biochem, I-53100 Siena, Italy

[10] Italian Natl Res Council, Inst Genet & Biophys Adriano Buzzati Traverso, Naples, Italy

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

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

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

[14] Leiden Univ, Med Ctr, Dept Endocrinol & Metab Dis, Leiden, Netherlands

[15] Univ Salamanca, Dept Med, Hosp Univ Salamanca, Serv Reumatol, E-37008 Salamanca, Spain

[16] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia

[17] Univ Western Australia, Med Res Ctr, Western Australian Inst Med Res, Crawley, WA, Australia

[18] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy

[19] Univ Salamanca, CSIC, Unidad Med Mol, Dept Med,Inst Biol Mol & Celular Canc, E-37008 Salamanca, Spain

[20] Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia

来源：

NATURE GENETICS | 2011年 / 43卷 / 07期

基金：

英国惠康基金;

关键词：

DC-STAMP; FAMILIAL AGGREGATION; GENETIC RISK; LARGE-SCALE; MUTATIONS; SQSTM1; EPIDEMIOLOGY; TNFRSF11A; VARIANTS; PROTEIN;

D O I：

10.1038/ng.845

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 characterized by focal abnormalities of bone remodeling. We previously identified variants at the CSF1, OPTN and TNFRSF11A loci as risk factors for PDB by genome-wide association study(1). Here we extended this study, identified three new loci and confirmed their association with PDB in 2,215 affected individuals (cases) and 4,370 controls from seven independent populations. The new associations were with rs5742915 within PML on 15q24 (odds ratio (OR) = 1.34, P = 1.6 x 10(-14)), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 x 10(-11)) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 x 10(-10)). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 x 10(-17)) with PDB. These seven loci explained similar to 13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.

引用

页码：685 / U104

页数：7

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