Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand.
Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand.
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DOI：
10.1002/art.24524
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发表时间：
2009-06
影响因子：
--
通讯作者：
Ioannidis, John P. A.
中科院分区：
文献类型：
--
作者：
Evangelou, Evangelos;Chapman, Kay;Meulenbelt, Ingrid;Karassa, Fotini B.;Loughlin, John;Carr, Andrew;Doherty, Michael;Doherty, Sally;Gomez-Reino, Juan J.;Gonzalez, Antonio;Halldorsson, Bjarni V.;Hauksson, Valdimar B.;Hofman, Albert;Hart, Deborah J.;Ikegawa, Shiro;Ingvarsson, Thorvaldur;Jiang, Qing;Jonsdottir, Ingileif;Jonsson, Helgi;Kerkhof, Hanneke J. M.;Kloppenburg, Margreet;Lane, Nancy E.;Li, Jia;Lories, Rik J.;van Meurs, Joyce B. J.;Nakki, Annu;Nevitt, Michael C.;Rodriguez-Lopez, Julio;Shi, Dongquan;Slagboom, Eline;Stefansson, Kari;Tsezou, Aspasia;Wallis, Gillian A.;Watson, Christopher M.;Spector, Tim D.;Uitterlinden, Andre G.;Valdes, Ana M.;Ioannidis, John P. A.
GDF 5和FRZB已被提出作为赋予骨关节炎（OA）易感性的遗传位点;然而，研究OA与GDF 5基因rs 143383多态性或FRZB基因rs7775和rs 288326多态性相关性的几项研究的结果相互矛盾或不确定。为了检验这些关联，我们对个体水平的数据进行了大规模的荟萃分析。14个团队提供了多态性与膝关节、髋关节和手部OA的数据。对于rs 143383，髋关节OA的病例和对照总数分别为5，789和7，850，膝关节OA为5，085和8，135，手部OA为4，040和4，792。对于rs7775，髋关节OA的样本量分别为4，352和10，843，膝关节OA的样本量分别为3，545和6，085，手部OA的样本量分别为4，010和5，151，对于rs 288326，髋关节OA的样本量分别为4，346和8，034，膝关节OA的样本量分别为3，595和6，106，手部OA的样本量分别为3，982和5，手OA 152对于每项单独的研究，计算已研究的每种OA表型的性别特异性比值比（OR）。使用固定效应和随机效应模型合成每个表型的OR，用于基于等位基因的效应，也用于FRZB的单倍型效应。rs 143383（1.15 [95%置信区间1.09-1.22]）（P = 9.4 × 10−7）显示了膝关节OA的显著随机效应总结OR，研究间无显著异质性。髋关节和手部OA的效应量估计值相似，但观察到较大的研究间异质性，统计学显著性为临界值（髋关节OA [P = 0.016]）或不存在（手部OA [P = 0.19]）。FRZB多态性和单倍型的分析没有发现任何统计学上显著的信号，除了rs 288326与髋关节OA的临界关联（P = 0.019）。GDF 5 rs 143383多态性与OA之间存在关联的证据非常强，但仅膝关节OA的遗传效应在不同人群中是一致的。这项合作分析的结果不支持FRZB rs7775或rs 288326对OA表型有任何相当大的遗传影响的观点。
GDF5 and FRZB have been proposed as genetic loci conferring susceptibility to osteoarthritis (OA); however, the results of several studies investigating the association of OA with the rs143383 polymorphism of the GDF5 gene or the rs7775 and rs288326 polymorphisms of the FRZB gene have been conflicting or inconclusive. To examine these associations, we performed a large-scale meta-analysis of individual-level data. Fourteen teams contributed data on polymorphisms and knee, hip, and hand OA. For rs143383, the total number of cases and controls, respectively, was 5,789 and 7,850 for hip OA, 5,085 and 8,135 for knee OA, and 4,040 and 4,792 for hand OA. For rs7775, the respective sample sizes were 4,352 and 10,843 for hip OA, 3,545 and 6,085 for knee OA, and 4,010 and 5,151 for hand OA, and for rs288326, they were 4,346 and 8,034 for hip OA, 3,595 and 6,106 for knee OA, and 3,982 and 5,152 for hand OA. For each individual study, sex-specific odds ratios (ORs) were calculated for each OA phenotype that had been investigated. The ORs for each phenotype were synthesized using both fixed-effects and random-effects models for allele-based effects, and also for haplotype effects for FRZB. A significant random-effects summary OR for knee OA was demonstrated for rs143383 (1.15 [95% confidence interval 1.09–1.22]) (P = 9.4 × 10−7), with no significant between-study heterogeneity. Estimates of effect sizes for hip and hand OA were similar, but a large between-study heterogeneity was observed, and statistical significance was borderline (for OA of the hip [P = 0.016]) or absent (for OA of the hand [P = 0.19]). Analyses for FRZB polymorphisms and haplotypes did not reveal any statistically significant signals, except for a borderline association of rs288326 with hip OA (P = 0.019). Evidence of an association between the GDF5 rs143383 polymorphism and OA is substantially strong, but the genetic effects are consistent across different populations only for knee OA. Findings of this collaborative analysis do not support the notion that FRZB rs7775 or rs288326 has any sizable genetic effect on OA phenotypes.
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影响因子：
--
作者：
ALTMAN, R;ALARCON, G;WOLFE, F
通讯作者：
WOLFE, F
报告的流行病学风险中的选择：经验评估。
影响因子：
15.8
作者：
Kavvoura FK;Liberopoulos G;Ioannidis JP
通讯作者：
Ioannidis JP
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N
影响因子：
3.5
作者：
Chapman, Kay;Takahashi, Atsushi;Ikegawa, Shiro
通讯作者：
Ikegawa, Shiro
影响因子：
5
作者：
Ioannidis, John P. A.
通讯作者：
Ioannidis, John P. A.