Rosemary Dargie

Publications (2)71.06 Total impact

• Source

  Available from: Fernando Gianfrancesco

  Article: 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, [......], 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
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  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.
  Nature Genetics 05/2011; 43(7):685-9. · 35.53 Impact Factor
• Source

  Available from: Gianluca Isaia

  Article: 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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  ABSTRACT: 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.
  Nature Genetics 06/2010; 42(6):520-4. · 35.53 Impact Factor