Regional meta-analysis of published data supports linkage of autism with markers on chromosome 7
Regional meta-analysis of published data supports linkage of autism with markers on chromosome 7
复制标题
DOI：
10.1038/sj/mp/4000922
复制
发表时间：
2002-01-01
影响因子：
11
通讯作者：
Gershon, ES
中科院分区：
文献类型：
--
作者：
Badner, JA;Gershon, ES
尽管对一个遗传性状的多重连锁扫描进行荟萃分析的概念并不新鲜，但由于在呈现连锁结果方面缺乏一致性，它可能很难应用于已公布的数据。在复杂遗传常见疾病中，有许多情况下，一项或两项研究符合全基因组显著或暗示连锁的标准，但其他几项研究甚至没有显示出与相同区域名义上的显著结果。解决研究结果之间差异的一种可能性是将几项研究的可用结果参数结合在一起。在这里，我们描述了一种区域荟萃分析方法，即多重扫描概率(MSP)，该方法可用于已发表的结果。它结合了个别研究报告的P值，然后根据包含最小P值的区域的大小对每个值进行校正。分析了MSP的功率和第I类误码率。I型错误率至少与单一基因组扫描的错误率一样低，因此可以应用全基因组显着性标准。当最重要的研究被纳入时，以及当该研究被用来定义感兴趣的区域然后被排除时，我们也证明了这种类型的荟萃分析的适当标准。在我们的模拟中，荟萃分析至少和汇集数据一样强大。最后，我们将这种荟萃分析方法应用到自闭症易感基因连锁的证据中，并证明了7q易感基因的证据。
Although the concept of meta-analysis of multiple linkage scans of a genetic trait is not new, it can be difficult to apply to published data given the lack of consistency in the presentation of linkage results. In complex inheritance common diseases, there are many instances where one or two studies meet genome-wide criteria for significant or suggestive linkage but several other studies do not show even nominally significant results with the same region. One possibility for resolving differences between study results would be to combine an available result parameter of several studies. We describe here a method of regional meta-analysis, the multiple-scan probability (MSP), which can be used on published results. It combines the reported P-values of individual studies, after correcting each value for the size of the region containing a minimum P-value. Analyses of the power of MSP and of its type I error rates are presented. The type I error rate is at least as low as that for a single genome scan and thus genome-wide significance criteria may be applied. We also demonstrate appropriate criteria for this type of meta-analysis when the most significant study is included, and when that study is used to define a region of interest and then excluded. In our simulations, meta-analysis is at least as powerful as pooling data. Finally, we apply this method of meta-analysis to the evidence for linkage of autism susceptibility loci and demonstrate evidence for a susceptibility locus at 7q.