Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Nat Genet. 2010 Jun;42(6):520-4. doi: 10.1038/ng.562. Epub 2010 May 2.
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.
佩吉特氏骨病（PDB）是一种常见的疾病，具有强烈的遗传成分，其特征是骨代谢的局部增加，在某些情况下是由 SQSTM1 突变引起的。为了确定其他易感基因，我们对 750 名没有 SQSTM1 突变的 PDB 患者（病例）和 1002 名对照进行了全基因组关联研究，并确定了三个候选疾病基因座，然后在 500 名病例和 535 名对照的独立组中进行了复制。最强的信号位于 CSF1 基因附近 1p13 上的 rs484959（P = 5.38 x 10(-24)）。在 OPTN 基因内的 rs1561570 上（P = 6.09 x 10(-13)）和在 TNFRSF11A 基因附近的 18q21 上的 rs3018362 上（P = 5.27 x 10(-13)）也观察到了显著的关联。这些研究为 PDB 的发病机制提供了新的见解，并确定 OPTN、CSF1 和 TNFRSF11A 为疾病易感性的候选基因。
