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; Kirsteen Goodman; Maria Luisa Brandi; Tim Cundy; Pui Yan Jenny Chung; Rosemary Dargie; Jean Pierre Devogelaer; Alberto Falchetti; William D. Fraser; Luigi Gennari; Fernando Gianfrancesco; Michael J. Hooper; Wim Van Hul; Gianluca Isaia; Geoff C. Nicholson; Ranuccio Nuti; Socrates Papapoulos; Javier Del Pino Montes; Thomas Ratajczak; Sarah L. Rea; Domenico Rendina; Rogelio Gonzalez-Sarmiento; Marco Di Stefano; Lynley C. Ward; John P. Walsh; Stuart H. Ralston

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
, Kirsteen Goodman
, Maria Luisa Brandi
, Tim Cundy
, Pui Yan Jenny Chung
, Rosemary Dargie
, Jean Pierre Devogelaer
, Alberto Falchetti
, William D. Fraser
, Luigi Gennari
, Fernando Gianfrancesco
, Michael J. Hooper
, Wim Van Hul
, Gianluca Isaia
, Geoff C. Nicholson
, Ranuccio Nuti
, Socrates Papapoulos

Javier Del Pino Montes, Thomas Ratajczak, Sarah L. Rea, Domenico Rendina, Rogelio Gonzalez-Sarmiento, Marco Di Stefano, Lynley C. Ward, John P. Walsh, Stuart H. Ralston

^*Corresponding author for this work

University of Edinburgh
University of Florence
The University of Auckland
University of Antwerp
NHS Greater Glasgow and Clyde
Université catholique de Louvain
Liverpool University Hospitals NHS Foundation Trust
University of Siena
National Research Council of Italy
The University of Sydney
University of Turin
University of Melbourne
Leiden University
Universidad de Salamanca
Sir Charles Gairdner Hospital
University of Western Australia
University of Naples Federico II
University of Western Australia

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

155 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
Issue number	7
DOIs	https://doi.org/10.1038/ng.845
Publication status	Published - Jul 2011
Externally published	Yes

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Albagha, O. M. E., Wani, S. E., Visconti, M. R., Alonso, N., Goodman, K., Brandi, M. L., Cundy, T., Chung, P. Y. J., Dargie, R., Devogelaer, J. P., Falchetti, A., Fraser, W. D., Gennari, L., Gianfrancesco, F., Hooper, M. J., Van Hul, W., Isaia, G., Nicholson, G. C., Nuti, R., ... Ralston, S. H. (2011). Genome-wide association identifies three new susceptibility loci for Paget's disease of bone. Nature Genetics, 43(7), 685-689. https://doi.org/10.1038/ng.845

@article{e28cd86f4bea469388f3f9335ef35bc4,

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.",

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

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",

number = "7",

}

Albagha, OME, Wani, SE, Visconti, MR, Alonso, N, Goodman, K, Brandi, ML, Cundy, T, Chung, PYJ, Dargie, R, Devogelaer, JP, Falchetti, A, Fraser, WD, Gennari, L, Gianfrancesco, F, Hooper, MJ, Van Hul, W, Isaia, G, Nicholson, GC, Nuti, R, Papapoulos, S, Montes, JDP, Ratajczak, T, Rea, SL, Rendina, D, Gonzalez-Sarmiento, R, Di Stefano, M, Ward, LC, Walsh, JP & Ralston, SH 2011, 'Genome-wide association identifies three new susceptibility loci for Paget's disease of bone', Nature Genetics, vol. 43, no. 7, 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 - Goodman, Kirsteen

AU - Brandi, Maria Luisa

AU - Cundy, Tim

AU - Chung, Pui Yan Jenny

AU - Dargie, Rosemary

AU - Devogelaer, Jean Pierre

AU - Falchetti, Alberto

AU - Fraser, William D.

AU - Gennari, Luigi

AU - Gianfrancesco, Fernando

AU - Hooper, Michael J.

AU - Van Hul, Wim

AU - Isaia, Gianluca

AU - Nicholson, Geoff C.

AU - Nuti, Ranuccio

AU - Papapoulos, Socrates

AU - Montes, Javier Del Pino

AU - Ratajczak, Thomas

AU - Rea, Sarah L.

AU - Rendina, Domenico

AU - Gonzalez-Sarmiento, Rogelio

AU - Di Stefano, Marco

AU - Ward, Lynley C.

AU - Walsh, John P.

AU - Ralston, Stuart H.

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.

UR - https://www.scopus.com/pages/publications/79959745220

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

IS - 7

ER -

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

Abstract

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