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

共 41 条

[1] Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone
Albagha, Omar M. E.
Visconti, Micaela R.
Alonso, Nerea
Langston, Anne L.
Cundy, Tim
Dargie, Rosemary
Dunlop, Malcolm G.
Fraser, William D.
Hooper, Michael J.
Isaia, Gianluca
Nicholson, Geoff C.
del Pino Montes, Javier
Gonzalez-Sarmiento, Rogelio
di Stefano, Marco
Tenesa, Albert
Walsh, John P.
Ralston, Stuart H.
[J]. NATURE GENETICS, 2010, 42 (06) : 520 - U26
[2] ProbABEL package for genome-wide association analysis of imputed data
Aulchenko, Yurii S.
Struchalin, Maksim V.
van Duijn, Cornelia M.
[J]. BMC BIOINFORMATICS, 2010, 11
[3] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
Burton, Paul R.
Clayton, David G.
Cardon, Lon R.
Craddock, Nick
Deloukas, Panos
Duncanson, Audrey
Kwiatkowski, Dominic P.
McCarthy, Mark I.
Ouwehand, Willem H.
Samani, Nilesh J.
Todd, John A.
Donnelly, Peter
Barrett, Jeffrey C.
Davison, Dan
Easton, Doug
Evans, David
Leung, Hin-Tak
Marchini, Jonathan L.
Morris, Andrew P.
Spencer, Chris C. A.
Tobin, Martin D.
Attwood, Antony P.
Boorman, James P.
Cant, Barbara
Everson, Ursula
Hussey, Judith M.
Jolley, Jennifer D.
Knight, Alexandra S.
Koch, Kerstin
Meech, Elizabeth
Nutland, Sarah
Prowse, Christopher V.
Stevens, Helen E.
Taylor, Niall C.
Walters, Graham R.
Walker, Neil M.
Watkins, Nicholas A.
Winzer, Thilo
Jones, Richard W.
McArdle, Wendy L.
Ring, Susan M.
Strachan, David P.
Pembrey, Marcus
Breen, Gerome
St Clair, David
Caesar, Sian
Gordon-Smith, Katherine
Jones, Lisa
Fraser, Christine
Green, Elain K.
[J]. NATURE, 2007, 447 (7145) : 661 - 678
[4] The majority of the genetic risk for Paget's disease of bone is explained by genetic variants close to the CSF1, OPTN, TM7SF4, and TNFRSF11A genes
Chung, Pui Yan Jenny
Beyens, Greet
Boonen, Steven
Papapoulos, Socrates
Geusens, Piet
Karperien, Marcel
Vanhoenacker, Filip
Verbruggen, Leon
Fransen, Erik
Van Offel, Jan
Goemaere, Stefan
Zmierczak, Hans-Georg
Westhovens, Rene
Devogelaer, Jean-Pierre
Van Hul, Wim
[J]. HUMAN GENETICS, 2010, 128 (06) : 615 - 626
[5] Population structure, differential bias and genomic control in a large-scale, case-control association study
Clayton, DG
Walker, NM
Smyth, DJ
Pask, R
Cooper, JD
Maier, LM
Smink, LJ
Lam, AC
Ovington, NR
Stevens, HE
Nutland, S
Howson, JMM
Faham, M
Moorhead, M
Jones, HB
Falkowski, M
Hardenbol, P
Willis, TD
Todd, JA
[J]. NATURE GENETICS, 2005, 37 (11) : 1243 - 1246
[6] The epidemiology of Paget's disease in Britain: Is the prevalence decreasing?
Cooper, C
Schafheutle, K
Dennison, E
Kellingray, S
Guyer, P
Barker, D
[J]. JOURNAL OF BONE AND MINERAL RESEARCH, 1999, 14 (02) : 192 - 197
[7] The role of prenylated small GTP-binding proteins in the regulation of osteoclast function
Coxon, FP
Rogers, MJ
[J]. CALCIFIED TISSUE INTERNATIONAL, 2003, 72 (01) : 80 - 84
[8] METAANALYSIS IN CLINICAL-TRIALS
DERSIMONIAN, R
LAIRD, N
[J]. CONTROLLED CLINICAL TRIALS, 1986, 7 (03): : 177 - 188
[9] Paget's disease of bone in the Netherlands: A population-based radiological and biochemical survey - The Rotterdam Study
Eekhoff, MEMW
van der Klift, M
Kroon, HM
Cooper, C
Hofman, A
Pols, HAP
Papapoulos, SE
[J]. JOURNAL OF BONE AND MINERAL RESEARCH, 2004, 19 (04) : 566 - 570
[10] Genetic Epidemiology of Paget's Disease of Bone in Italy: sequestosome1/p62 Gene Mutational Test and Haplotype Analysis at 5q35 in a Large Representative Series of Sporadic and Familial Italian Cases of Paget's Disease of Bone
Falchetti, Alberto
Di Stefano, Marco
Marini, Francesca
Ortolani, Sergio
Ulivieri, Massimo Fabio
Bergui, Simona
Masi, Laura
Cepollaro, Chiara
Benucci, Maurizio
Di Munno, Ombretta
Rossini, Maurizio
Adami, Silvano
Del Puente, Antonio
Isaia, Giancarlo
Torricelli, Francesca
Brandi, Maria Luisa
[J]. CALCIFIED TISSUE INTERNATIONAL, 2009, 84 (01) : 20 - 37

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