Non-Replication of Association for Six Polymorphisms From Meta-Analysis of Genome-Wide Association Studies of Parkinson's Disease: Large-Scale Collaborative Study
Non-Replication of Association for Six Polymorphisms From Meta-Analysis of Genome-Wide Association Studies of Parkinson's Disease: Large-Scale Collaborative Study
复制标题
DOI：
10.1002/ajmg.b.30980
复制
发表时间：
2010-01-01
影响因子：
2.8
通讯作者：
Ioannidis, John P. A.
中科院分区：
文献类型：
--
作者：
Evangelou, Evangelos;Maraganore, Demetrius M.;Ioannidis, John P. A.
早期关于帕金森病 (PD) 的全基因组关联 (GWA) 研究未能产生结论性的、可复制的关联信号，这可能是由于样本量有限。我们的目的是调查前两项 GWA 调查的荟萃分析得出的关联信号是否可以在不同人群中复制。我们检查了六个单核苷酸多态性 (SNP)（rs1000291、rs1865997、rs2241743、rs2282048、rs2313982 和 rs3018626），这些多态性在之前对原始 GWA 研究的分析中提出的三种不同策略中至少有两种已达到名义显着性。来自“帕金森病遗传流行病学”（GEOPD）联盟的研究人员受邀参加这项研究。十个团队贡献了 3,458 个 PD 病例和 3,719 个对照的复制数据。还考虑了之前发布的两个 GWA（599 个 PD 病例、592 个对照和 443 个兄弟姐妹对）的数据。所有数据均使用固定效应模型和随机效应模型进行合成。当包括所有数据时，随机效应的等位基因比值比总结范围为 0.97 至 1.09。复制数据集（不包括原始 GWA 数据）的汇总估计非常接近 1.00（范围 0.98-1.09），并且没有任何影响在名义上具有统计显着性。复制数据集的结果与 GWA 数据显着不同。我们的数据不支持这六个 SNP 中任何一个反映 PD 易感性标记的证据。 GWA 平台需要更强的统计显着性信号才能有大量复制机会。特别是在 PD 遗传学方面，这需要更大规模的 GWA 研究，或许还需要新颖的分析技术。 (C) 2009 Wiley-Liss, Inc.
Early genome-wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta-analysis of the first two GWA investigations might be replicable in different populations. We examined six single-nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the "Genetic Epidemiology of Parkinson's Disease" (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98-1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques. (C) 2009 Wiley-Liss, Inc.