Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone

Omar M E Albagha, Micaela R Visconti, Nerea Alonso, Anne L Langston, Tim Cundy, Rosemary Dargie, Malcolm G Dunlop, William D Fraser, Michael J Hooper, Gianluca Isaia, Geoff C Nicholson, Javier del Pino Montes, Rogelio Gonzalez-Sarmiento, Marco di Stefano, Albert Tenesa, John P Walsh, Stuart H Ralston

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237 Citations (Scopus)


Paget's disease of bone (PDB) is a common disorder with a strong genetic component characterized by focal increases in bone turnover, which in some cases is caused by mutations in SQSTM1. To identify additional susceptibility genes, we performed a genome-wide association study in 750 individuals with PDB (cases) without SQSTM1 mutations and 1,002 controls and identified three candidate disease loci, which were then replicated in an independent set of 500 cases and 535 controls. The strongest signal was with rs484959 on 1p13 near the CSF1 gene (P = 5.38 x 10(-24)). Significant associations were also observed with rs1561570 on 10p13 within the OPTN gene (P = 6.09 x 10(-13)) and with rs3018362 on 18q21 near the TNFRSF11A gene (P = 5.27 x 10(-13)). These studies provide new insights into the pathogenesis of PDB and identify OPTN, CSF1 and TNFRSF11A as candidate genes for disease susceptibility.
Original languageEnglish
Pages (from-to)520-524
Number of pages5
JournalNature Genetics
Issue number6
Publication statusPublished - Jun 2010


  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Macrophage Colony-Stimulating Factor
  • Osteitis Deformans
  • Polymorphism, Single Nucleotide
  • Receptor Activator of Nuclear Factor-kappa B
  • Risk Factors
  • Transcription Factor TFIIIA

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