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

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142 Citations (Scopus)


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 languageEnglish
Pages (from-to)685-9
Number of pages5
JournalNature Genetics
Issue number7
Publication statusPublished - Jul 2011


  • 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

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