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

Omar Al Bagha, 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, Rogelio Gonzalez-Sarmiento, Marco Di Stefano, Lynley C. Ward, John P. Walsh, Stuart H. Ralston

Research output: Contribution to journalArticle

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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 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 languageEnglish
Pages (from-to)685-689
Number of pages5
JournalNature Genetics
Volume43
Issue number7
DOIs
Publication statusPublished - Jul 2011
Externally publishedYes

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Osteitis Deformans
Genome
Odds Ratio
Bone Remodeling
Genome-Wide Association Study
Population

ASJC Scopus subject areas

  • Genetics

Cite this

Al Bagha, O., Wani, S. E., Visconti, M. R., Alonso, N., Goodman, K., Brandi, M. L., ... 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

Genome-wide association identifies three new susceptibility loci for Paget's disease of bone. / Al Bagha, Omar; Wani, Sachin E.; Visconti, Micaela R.; Alonso, Nerea; Goodman, Kirsteen; Brandi, Maria Luisa; Cundy, Tim; Chung, Pui Yan Jenny; Dargie, Rosemary; Devogelaer, Jean Pierre; Falchetti, Alberto; Fraser, William D.; Gennari, Luigi; Gianfrancesco, Fernando; Hooper, Michael J.; Van Hul, Wim; Isaia, Gianluca; Nicholson, Geoff C.; Nuti, Ranuccio; Papapoulos, Socrates; Montes, Javier Del Pino; Ratajczak, Thomas; Rea, Sarah L.; Rendina, Domenico; Gonzalez-Sarmiento, Rogelio; Di Stefano, Marco; Ward, Lynley C.; Walsh, John P.; Ralston, Stuart H.

In: Nature Genetics, Vol. 43, No. 7, 07.2011, p. 685-689.

Research output: Contribution to journalArticle

Al Bagha, O, 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
Al Bagha, Omar ; Wani, Sachin E. ; Visconti, Micaela R. ; Alonso, Nerea ; Goodman, Kirsteen ; Brandi, Maria Luisa ; Cundy, Tim ; Chung, Pui Yan Jenny ; Dargie, Rosemary ; Devogelaer, Jean Pierre ; Falchetti, Alberto ; Fraser, William D. ; Gennari, Luigi ; Gianfrancesco, Fernando ; Hooper, Michael J. ; Van Hul, Wim ; Isaia, Gianluca ; Nicholson, Geoff C. ; Nuti, Ranuccio ; Papapoulos, Socrates ; Montes, Javier Del Pino ; Ratajczak, Thomas ; Rea, Sarah L. ; Rendina, Domenico ; Gonzalez-Sarmiento, Rogelio ; Di Stefano, Marco ; Ward, Lynley C. ; Walsh, John P. ; Ralston, Stuart H. / Genome-wide association identifies three new susceptibility loci for Paget's disease of bone. In: Nature Genetics. 2011 ; Vol. 43, No. 7. pp. 685-689.
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AU - Al Bagha, Omar

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.

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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.

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