全基因组关联分析鉴定出三个新的骨骼 Pagets 病易感性位点。
Genome-wide association identifies three new susceptibility loci for Paget's disease of bone.
机构信息
Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
出版信息
Nat Genet. 2011 May 29;43(7):685-9. doi: 10.1038/ng.845.
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.
佩吉特氏骨病（PDB）是一种常见的骨骼重塑局灶性异常疾病。我们之前通过全基因组关联研究发现 CSF1、OPTN 和 TNFRSF11A 基因座的变异是 PDB 的风险因素。在此，我们通过对来自七个独立群体的 2215 名 PDB 患者（病例）和 4370 名对照者进行研究，扩展了这项研究，鉴定出三个新的基因座，并证实了它们与 PDB 的关联。新的关联是位于 15q24 的 PML 内的 rs5742915（比值比（OR）=1.34，P=1.6×10(-14))，位于 14q32 的 RIN3 内的 rs10498635（OR=1.44，P=2.55×10(-11))，以及位于 7q33 的 NUP205 内的 rs4294134（OR=1.45，P=8.45×10(-10))。我们的数据还证实了 TM7SF4（rs2458413，OR=1.40，P=7.38×10(-17))与 PDB 的关联。这七个基因座解释了 PDB 约 13%的家族风险。这些研究为 PDB 的遗传结构和病理生理学提供了新的见解。
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