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
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DOI：
10.1038/sj.mp.4000922
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发表时间：
2002
影响因子：
11
通讯作者：
J. Badner;E. Gershon
中科院分区：
文献类型：
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作者：
J. Badner;E. Gershon
虽然对遗传性状的多个连锁扫描进行荟萃分析的概念并不新鲜，但由于连锁结果的呈现缺乏一致性，因此很难应用于已发表的数据。在复杂的遗传常见病中，有许多情况下，一两个研究符合全基因组标准，具有显著或暗示性的联系，但其他一些研究在同一区域甚至没有显示出名义上显著的结果。解决研究结果之间差异的一种可能性是将几个研究的可用结果参数结合起来。我们在这里描述了一种区域荟萃分析方法，多重扫描概率（MSP），它可以用于已发表的结果。在根据包含最小p值的区域的大小对每个值进行校正后，它结合了个别研究报告的p值。对MSP的功率和I型错误率进行了分析。I型错误率至少与单基因组扫描的错误率一样低，因此可以应用全基因组显著性标准。当最重要的研究被纳入时，以及当该研究被用来定义一个感兴趣的区域然后被排除时，我们还展示了这种类型的元分析的适当标准。在我们的模拟中，元分析至少与汇集数据一样强大。最后，我们将这种方法应用于自闭症易感位点连锁的证据，并证明了7q易感位点的证据。
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.