Effects of updating linkage evidence across subsets of data: Reanalysis of the autism genetic resource exchange data set
Effects of updating linkage evidence across subsets of data: Reanalysis of the autism genetic resource exchange data set
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DOI：
10.1086/429345
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发表时间：
2005-04-01
影响因子：
9.8
通讯作者：
Vieland, VJ
中科院分区：
文献类型：
--
作者：
Bartlett, CW;Goedken, R;Vieland, VJ
自闭症连锁研究的结果很难在不同的研究小组之间进行解释，这促使人们使用不断增加的样本量来提高功效。然而，事实上，通过汇集不同的集合进行单一分析来增加样本量可能不会增加面对遗传异质性的功效。在这里，我们应用后验概率的链接（PPL），一种专门设计用于分析多个异质数据集的方法，自闭症遗传资源交换收集的家庭通过分析六个临床定义的子集的数据和更新PPL顺序的子集。我们的研究结果表明，连锁的1号染色体，这是以前被忽视的一个很大的可能性，我们的研究结果还提供了一个可能的父母的起源在17q11基因座的影响，以前在这个样本中描述的进一步表征。这一分析表明，在连锁分析中处理异质性的方式可以显着影响连锁研究的总体结论。
Results of autism linkage studies have been difficult to interpret across research groups, prompting the use of ever-increasing sample sizes to increase power. However, increasing sample size by pooling disparate collections for a single analysis may, in fact, not increase power in the face of genetic heterogeneity. Here, we applied the posterior probability of linkage (PPL), a method designed specifically to analyze multiple heterogeneous data sets, to the Autism Genetic Resource Exchange collection of families by analyzing six clinically defined subsets of the data and updating the PPL sequentially over the subsets. Our results indicate a substantial probability of linkage to chromosome 1, which had been previously overlooked; our findings also provide a further characterization of the possible parent-of-origin effects at the 17q11 locus that were previously described in this sample. This analysis illustrates that the way in which heterogeneity is addressed in linkage analysis can dramatically affect the overall conclusions of a linkage study.