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

Omar M.E. Albagha; Sachin E. Wani; Micaela R. Visconti; Nerea Alonso; Stuart H. Ralston; Kirsteen Goodman; Maria Luisa Brandi; Alberto Falchetti; Tim Cundy; Pui Yan Jenny Chung; Wim Van Hul; Rosemary Dargie; Jean Pierre Devogelaer; William D. Fraser; Luigi Gennari; Ranuccio Nuti; Fernando Gianfrancesco; Michael J. Hooper; Gianluca Isaia; Marco Di Stefano; Geoff C. Nicholson; Socrates Papapoulos; Javier Del Pino Montes; Thomas Ratajczak; Sarah L. Rea; Lynley C. Ward; John P. Walsh; Domenico Rendina; Rogelio Gonzalez-Sarmiento; The Genetic Determinants of Paget's Disease (GDPD) Consortium

doi:10.1038/ng.845

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

Omar M.E. Albagha^*, Sachin E. Wani, Micaela R. Visconti, Nerea Alonso, Stuart H. Ralston, Kirsteen Goodman, Maria Luisa Brandi, Alberto Falchetti, Tim Cundy, Pui Yan Jenny Chung, Wim Van Hul, Rosemary Dargie, Jean Pierre Devogelaer, William D. Fraser, Luigi Gennari, Ranuccio Nuti, Fernando Gianfrancesco, Michael J. Hooper, Gianluca Isaia, Marco Di StefanoGeoff C. Nicholson, Socrates Papapoulos, Javier Del Pino Montes, Thomas Ratajczak, Sarah L. Rea, Lynley C. Ward, John P. Walsh, Domenico Rendina, Rogelio Gonzalez-Sarmiento, The Genetic Determinants of Paget's Disease (GDPD) Consortium

^*Corresponding author for this work

NMAHP

Research output: Contribution to journal › Article › peer-review

146 Citations (Scopus)

Abstract

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. 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 × 10 ^-14), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 × 10^-11) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 × 10^-10). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 × 10^-17) with PDB. These seven loci explained μ13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.

Original language	English
Pages (from-to)	685-689
Number of pages	5
Journal	Nature Genetics
Volume	43
Early online date	29 May 2011
DOIs	https://doi.org/10.1038/ng.845
Publication status	Published - Jul 2011

Keywords

genetic predisposition to disease
genome-wide association studies
Paget disease

ASJC Scopus subject areas

Genetics

Documents and Links

10.1038/ng.845

Cite this

Albagha, O. M. E., Wani, S. E., Visconti, M. R., Alonso, N., Ralston, S. H., Goodman, K., Brandi, M. L., Falchetti, A., Cundy, T., Chung, P. Y. J., Van Hul, W., Dargie, R., Devogelaer, J. P., Fraser, W. D., Gennari, L., Nuti, R., Gianfrancesco, F., Hooper, M. J., Isaia, G., ... The Genetic Determinants of Paget's Disease (GDPD) Consortium (2011). Genome-wide association identifies three new susceptibility loci for Paget's disease of bone. Nature Genetics, 43, 685-689. https://doi.org/10.1038/ng.845

@article{65231038a968439497374b804e611cb5,

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

abstract = "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. 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 × 10 -14), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 × 10-11) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 × 10-10). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 × 10-17) with PDB. These seven loci explained μ13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.",

keywords = "genetic predisposition to disease, genome-wide association studies, Paget disease",

author = "Albagha, {Omar M.E.} and Wani, {Sachin E.} and Visconti, {Micaela R.} and Nerea Alonso and Ralston, {Stuart H.} and Kirsteen Goodman and Brandi, {Maria Luisa} and Alberto Falchetti and Tim Cundy and Chung, {Pui Yan Jenny} and {Van Hul}, Wim and Rosemary Dargie and Devogelaer, {Jean Pierre} and Fraser, {William D.} and Luigi Gennari and Ranuccio Nuti and Fernando Gianfrancesco and Hooper, {Michael J.} and Gianluca Isaia and {Di Stefano}, Marco and Nicholson, {Geoff C.} and Socrates Papapoulos and Montes, {Javier Del Pino} and Thomas Ratajczak and Rea, {Sarah L.} and Ward, {Lynley C.} and Walsh, {John P.} and Domenico Rendina and Rogelio Gonzalez-Sarmiento and {The Genetic Determinants of Paget's Disease (GDPD) Consortium}",

year = "2011",

month = jul,

doi = "10.1038/ng.845",

language = "English",

volume = "43",

pages = "685--689",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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Albagha, OME, Wani, SE, Visconti, MR, Alonso, N, Ralston, SH, Goodman, K, Brandi, ML, Falchetti, A, Cundy, T, Chung, PYJ, Van Hul, W, Dargie, R, Devogelaer, JP, Fraser, WD, Gennari, L, Nuti, R, Gianfrancesco, F, Hooper, MJ, Isaia, G, Di Stefano, M, Nicholson, GC, Papapoulos, S, Montes, JDP, Ratajczak, T, Rea, SL, Ward, LC, Walsh, JP, Rendina, D, Gonzalez-Sarmiento, R & The Genetic Determinants of Paget's Disease (GDPD) Consortium 2011, 'Genome-wide association identifies three new susceptibility loci for Paget's disease of bone', Nature Genetics, vol. 43, pp. 685-689. https://doi.org/10.1038/ng.845

TY - JOUR

T1 - Genome-wide association identifies three new susceptibility loci for Paget's disease of bone

AU - Albagha, Omar M.E.

AU - Wani, Sachin E.

AU - Visconti, Micaela R.

AU - Alonso, Nerea

AU - Ralston, Stuart H.

AU - Goodman, Kirsteen

AU - Brandi, Maria Luisa

AU - Falchetti, Alberto

AU - Cundy, Tim

AU - Chung, Pui Yan Jenny

AU - Van Hul, Wim

AU - Dargie, Rosemary

AU - Devogelaer, Jean Pierre

AU - Fraser, William D.

AU - Gennari, Luigi

AU - Nuti, Ranuccio

AU - Gianfrancesco, Fernando

AU - Hooper, Michael J.

AU - Isaia, Gianluca

AU - Di Stefano, Marco

AU - Nicholson, Geoff C.

AU - Papapoulos, Socrates

AU - Montes, Javier Del Pino

AU - Ratajczak, Thomas

AU - Rea, Sarah L.

AU - Ward, Lynley C.

AU - Walsh, John P.

AU - Rendina, Domenico

AU - Gonzalez-Sarmiento, Rogelio

AU - The Genetic Determinants of Paget's Disease (GDPD) Consortium

PY - 2011/7

Y1 - 2011/7

N2 - 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. 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 × 10 -14), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 × 10-11) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 × 10-10). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 × 10-17) with PDB. These seven loci explained μ13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.

AB - 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. 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 × 10 -14), rs10498635 within RIN3 on 14q32 (OR = 1.44, P = 2.55 × 10-11) and rs4294134 within NUP205 on 7q33 (OR = 1.45, P = 8.45 × 10-10). Our data also confirmed the association of TM7SF4 (rs2458413, OR = 1.40, P = 7.38 × 10-17) with PDB. These seven loci explained μ13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.

KW - genetic predisposition to disease

KW - genome-wide association studies

KW - Paget disease

U2 - 10.1038/ng.845

DO - 10.1038/ng.845

M3 - Article

C2 - 21623375

AN - SCOPUS:79959745220

SN - 1061-4036

VL - 43

SP - 685

EP - 689

JO - Nature Genetics

JF - Nature Genetics

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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