Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone
Open Access
- 2 May 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 42 (6), 520-524
- https://doi.org/10.1038/ng.562
Abstract
Stuart Ralston and colleagues report results of a genome-wide association study for Paget's disease of bone. Their work identifies common variants at three loci associated with risk of this disease. 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 × 10−24). Significant associations were also observed with rs1561570 on 10p13 within the OPTN gene (P = 6.09 × 10−13) and with rs3018362 on 18q21 near the TNFRSF11A gene (P = 5.27 × 10−13). These studies provide new insights into the pathogenesis of PDB and identify OPTN, CSF1 and TNFRSF11A as candidate genes for disease susceptibility.This publication has 43 references indexed in Scilit:
- Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studiesNature Genetics, 2009
- Genes mirror geography within EuropeNature, 2008
- Long-Range LD Can Confound Genome Scans in Admixed PopulationsAmerican Journal of Human Genetics, 2008
- Multiple Genetic Loci for Bone Mineral Density and FracturesThe New England Journal of Medicine, 2008
- Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21Nature Genetics, 2008
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controlsNature, 2007
- Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesisNature Genetics, 2007
- Haploview: analysis and visualization of LD and haplotype mapsBioinformatics, 2004
- Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing proteinNature Genetics, 2004