Genome-wide Association Identifies Three New Susceptibility Loci for Paget's Disease of Bone

Overview

Journal Nat Genet

Specialty Genetics

Date 2011 May 31

PMID 21623375

Citations 69

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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