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; 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, 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, Genetic Determinants of Paget's Disease (GDPD) Consortium

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

145 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 ∼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)	685-9
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

Keywords

Aged
Asian Continental Ancestry Group
Case-Control Studies
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 7
Female
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Osteitis Deformans
Polymorphism, Single Nucleotide
Prognosis
Risk Factors

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.845

Cite this

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., ... 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(7), 685-9. https://doi.org/10.1038/ng.845

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

keywords = "Aged, Asian Continental Ancestry Group, Case-Control Studies, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 7, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Osteitis Deformans, Polymorphism, Single Nucleotide, Prognosis, Risk Factors",

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 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} and {Genetic Determinants of Paget's Disease (GDPD) Consortium}",

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month = jul,

doi = "10.1038/ng.845",

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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, Montes, JDP, Ratajczak, T, Rea, SL, Rendina, D, Gonzalez-Sarmiento, R, Di Stefano, M, Ward, LC, Walsh, JP, Ralston, SH & 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, no. 7, pp. 685-9. 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

AU - 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 ∼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 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 ∼13% of the familial risk of PDB. These studies provide new insights into the genetic architecture and pathophysiology of PDB.

KW - Aged

KW - Asian Continental Ancestry Group

KW - Case-Control Studies

KW - Chromosomes, Human, Pair 15

KW - Chromosomes, Human, Pair 7

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Male

KW - Osteitis Deformans

KW - Polymorphism, Single Nucleotide

KW - Prognosis

KW - Risk Factors

U2 - 10.1038/ng.845

DO - 10.1038/ng.845

M3 - Article

C2 - 21623375

VL - 43

SP - 685

EP - 689

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -