Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone.
Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone.
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全基因组关联研究将CSF1，OPTN和TNFRSF11A的变体确定为Paget骨骼疾病的遗传危险因素。
作者：
佩吉特骨病（PDB）是一种常见的疾病，具有强烈的遗传成分，其特征在于骨转换的局灶性增加，在某些情况下由SQSTM 1突变引起。为了确定额外的易感基因，我们在750例没有SQSTM 1突变的PDB病例和1002例对照中进行了全基因组关联研究，并确定了该疾病的三个候选基因座，这些基因座在500例病例和535例对照的独立组中重复。最强的信号是靠近CSF 1基因的1p13上的rs484959（P = 5.38 × 10−24），还观察到与OPTN基因内10p13上的rs1561570（P = 6.09 × 10−13）和靠近TNFRSF11A基因的18q21上的rs3018362（P = 5.27 × 10−13）的显著关联。这些研究为PDB的发病机制提供了新的见解，并将OPTN，CSF 1和TNFRSF11A确定为疾病易感性的新候选基因。
Paget’s disease of bone (PDB) is a common disorder with a strong genetic component characterised by focal increases in bone turnover which in some cases is caused by SQSTM1 mutations. To identify additional susceptibility genes we performed a genome wide association study in 750 PDB cases without SQSTM1 mutations and 1002 controls and identified three candidate loci for the disease which were replicated in an independent set of 500 cases and 535 controls. The strongest signal was with rs484959 on 1p13 close to the CSF1 gene (P = 5.38 × 10−24) and significant associations were also observed with rs1561570 on 10p13 within the OPTN gene (P = 6.09 × 10−13) and with rs3018362 on 18q21 close to 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 novel candidate genes for disease susceptibility.
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影响因子：
30.8
作者：
Rivadeneira, Fernando;Styrkarsdottir, Unnur;Estrada, Karol;Halldorsson, Bjarni V.;Hsu, Yi-Hsiang;Richards, J. Brent;Zillikens, M. Carola;Kavvoura, Fotini K.;Amin, Najaf;Aulchenko, Yurii S.;Cupples, L. Adrienne;Deloukas, Panagiotis;Demissie, Serkalem;Grundberg, Elin;Hofman, Albert;Kong, Augustine;Karasik, David;van Meurs, Joyce B.;Oostra, Ben;Pastinen, Tomi;Pols, Huibert A. P.;Sigurdsson, Gunnar;Soranzo, Nicole;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Williams, Frances M. K.;Wilson, Scott G.;Zhou, Yanhua;Ralston, Stuart H.;van Duijn, Cornelia M.;Spector, Timothy;Kiel, Douglas P.;Stefansson, Kari;Ioannidis, John P. A.;Uitterlinden, Andre G.
通讯作者：
Uitterlinden, Andre G.
影响因子：
56.9
作者：
Rezaie, T;Child, A;Sarfarazi, M
通讯作者：
Sarfarazi, M
影响因子：
6.2
作者：
Cooper, C;Schafheutle, K;Barker, D
通讯作者：
Barker, D
影响因子：
30.8
作者：
Clayton, DG;Walker, NM;Todd, JA
通讯作者：
Todd, JA
影响因子：
9.8
作者：
Hocking, LJ;Herbert, CA;Ralston, SH
通讯作者：
Ralston, SH