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; Roglio Gonzalez-Sarmiento; Marco Di Stefano; Lynley C. Ward; John P. Walsh; Stuart H. Ralston; Hermanus Bernardus Johannes Karperien

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 PapapoulosJavier del Pino Montes, Thomas Ratajczak, Sarah L. Rea, Domenico Rendina, Roglio Gonzalez-Sarmiento, Marco Di Stefano, Lynley C. Ward, John P. Walsh, Stuart H. Ralston, Hermanus Bernardus Johannes Karperien

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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 study1. 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 ~13% 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
Journal	Nature genetics
Volume	43
Issue number	7
DOIs	https://doi.org/10.1038/ng.845
Publication status	Published - 2011

Keywords

METIS-284398
IR-104384

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10.1038/ng.845

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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., ... Karperien, H. B. J. (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{db63c508668f42759ac420fbd0ae0322,

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 study1. 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 ~13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.",

keywords = "METIS-284398, IR-104384",

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 Jean-Pierre Devogelaer 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 {del Pino Montes}, Javier and Thomas Ratajczak and Rea, {Sarah L.} and Domenico Rendina and Roglio Gonzalez-Sarmiento and {Di Stefano}, Marco and Ward, {Lynley C.} and Walsh, {John P.} and Ralston, {Stuart H.} and Karperien, {Hermanus Bernardus Johannes}",

note = "Karperien is lid van GDPG consortium. dit is als auteur opgenomen en hij staat onder deze noemer vermeld als auteur in de acknowledgements. ",

year = "2011",

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, J-P, Falchetti, A, Fraser, WD, Gennari, L, Gianfrancesco, F, Hooper, MJ, van Hul, W, Isaia, G, Nicholson, GC, Nuti, R, Papapoulos, S, del Pino Montes, J, Ratajczak, T, Rea, SL, Rendina, D, Gonzalez-Sarmiento, R, Di Stefano, M, Ward, LC, Walsh, JP, Ralston, SH & Karperien, HBJ 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 - del Pino Montes, Javier

AU - Ratajczak, Thomas

AU - Rea, Sarah L.

AU - Rendina, Domenico

AU - Gonzalez-Sarmiento, Roglio

AU - Di Stefano, Marco

AU - Ward, Lynley C.

AU - Walsh, John P.

AU - Ralston, Stuart H.

AU - Karperien, Hermanus Bernardus Johannes

N1 - Karperien is lid van GDPG consortium. dit is als auteur opgenomen en hij staat onder deze noemer vermeld als auteur in de acknowledgements.

PY - 2011

Y1 - 2011

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 study1. 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 ~13% 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 study1. 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 ~13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.

KW - METIS-284398

KW - IR-104384

U2 - 10.1038/ng.845

DO - 10.1038/ng.845

M3 - Article

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

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