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.
authors.affiliation: Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK. omar.albagha@ed.ac.uk
authors.forename: Omar M E
authors.initials: OM
authors.lastname: Albagha
authors.forename: Sachin E
authors.initials: SE
authors.lastname: Wani
authors.forename: Micaela R
authors.initials: MR
authors.lastname: Visconti
authors.forename: Nerea
authors.initials: N
authors.lastname: Alonso
authors.forename: Kirsteen
authors.initials: K
authors.lastname: Goodman
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
authors.forename: Tim
authors.initials: T
authors.lastname: Cundy
authors.forename: Pui Yan Jenny
authors.initials: PY
authors.lastname: Chung
authors.forename: Rosemary
authors.initials: R
authors.lastname: Dargie
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Devogelaer
authors.forename: Alberto
authors.initials: A
authors.lastname: Falchetti
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.forename: Luigi
authors.initials: L
authors.lastname: Gennari
authors.forename: Fernando
authors.initials: F
authors.lastname: Gianfrancesco
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hooper
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hul
authors.forename: Gianluca
authors.initials: G
authors.lastname: Isaia
authors.forename: Geoff C
authors.initials: GC
authors.lastname: Nicholson
authors.forename: Ranuccio
authors.initials: R
authors.lastname: Nuti
authors.forename: Socrates
authors.initials: S
authors.lastname: Papapoulos
authors.forename: Javier del Pino
authors.initials: Jdel P
authors.lastname: Montes
authors.forename: Thomas
authors.initials: T
authors.lastname: Ratajczak
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rea
authors.forename: Domenico
authors.initials: D
authors.lastname: Rendina
authors.forename: Rogelio
authors.initials: R
authors.lastname: Gonzalez-Sarmiento
authors.forename: Marco
authors.initials: M
authors.lastname: Di Stefano
authors.forename: Lynley C
authors.initials: LC
authors.lastname: Ward
authors.forename: John P
authors.initials: JP
authors.lastname: Walsh
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010001:Osteitis Deformans / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012307:Risk Factors