Ch'ng Carolyn, Kwok Willie, Rogic Sanja, Pavlidis Paul
Graduate Program in Bioinformatics, University of British Columbia, Vancouver, Canada, V6T 1Z4 (C.C.).
Center for High Throughput Biology, University of British Columbia, Vancouver, Canada, V6T 1Z4 (C.C., W.K., S.R., P.P.).
Autism Res. 2015 Oct;8(5):593-608. doi: 10.1002/aur.1475. Epub 2015 Feb 26.
Autism spectrum disorders (ASD) are clinically heterogeneous and biologically complex. In general it remains unclear, what biological factors lead to changes in the brains of autistic individuals. A considerable number of transcriptome analyses have been performed in attempts to address this question, but their findings lack a clear consensus. As a result, each of these individual studies has not led to any significant advance in understanding the autistic phenotype as a whole. Here, we report a meta-analysis of more than 1000 microarrays across twelve independent studies on expression changes in ASD compared to unaffected individuals, in both blood and brain tissues. We identified a number of known and novel genes that are consistently differentially expressed across three studies of the brain (71 samples in total). A subset of the highly ranked genes is suggestive of effects on mitochondrial function. In blood, consistent changes were more difficult to identify, despite individual studies tending to exhibit larger effects than the brain studies. Our results are the strongest evidence to date of a common transcriptome signature in the brains of individuals with ASD.
自闭症谱系障碍（ASD）在临床上具有异质性，生物学上也很复杂。总体而言，导致自闭症个体大脑发生变化的生物学因素仍不清楚。为了解决这个问题，人们已经进行了大量的转录组分析，但研究结果缺乏明确的共识。因此，这些个体研究中的每一项都没有在整体上对自闭症表型的理解取得任何重大进展。在这里，我们报告了一项对1000多个微阵列的荟萃分析，这些微阵列来自12项关于ASD与未受影响个体相比在血液和脑组织中表达变化的独立研究。我们确定了一些已知和新的基因，这些基因在三项大脑研究（总共71个样本）中始终存在差异表达。排名靠前的一部分基因提示对线粒体功能有影响。在血液中，尽管个别研究往往比大脑研究表现出更大的影响，但一致的变化更难识别。我们的结果是迄今为止关于自闭症个体大脑中存在共同转录组特征的最有力证据。
