Probing the Association between Early Evolutionary Markers and Schizophrenia.
Probing the Association between Early Evolutionary Markers and Schizophrenia.
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DOI：
10.1371/journal.pone.0169227
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Andreassen OA
中科院分区：
文献类型：
--
作者：
Srinivasan S;Bettella F;Hassani S;Wang Y;Witoelar A;Schork AJ;Thompson WK;Collier DA;Desikan RS;Melle I;Dale AM;Djurovic S;Andreassen OA
精神分裂症被认为是人类进化的副产品，是我们语言、创造性思维和认知能力的妥协，因此，本质上是一种人类疾病。它在人类进化过程中的起源时间仍然不清楚。在这里，我们研究了人类早期进化的几个标志物及其与精神分裂症遗传风险的关系。我们通过分析精神分裂症和其他人类表型的全基因组关联研究，在一个适合多基因结构的统计框架中测试了精神分裂症的进化假说。我们分析了进化代理措施：人类加速区域，片段重复和ohnologs，代表人类进化的各个时期与精神分裂症相关的人类基因组位点的重叠。多基因富集图表明，在人类加速区域，分段重复和ohnologs精神分裂症协会的患病率较高。然而，富集主要是由连锁不平衡，特别是与功能元件，如内含子和非翻译区。我们的研究结果并没有提供明确的证据表明早期人类进化的标志物更可能与精神分裂症有关。虽然与精神分裂症相关的SNP在HAR、Ohno和SD区域富集，但富集似乎是通过与已知基因组富集类别的联系介导的。结合之前的研究结果，这些发现表明，精神分裂症的风险可能主要是在人类进化过程中最近发展起来的。
Schizophrenia is suggested to be a by-product of the evolution in humans, a compromise for our language, creative thinking and cognitive abilities, and thus, essentially, a human disorder. The time of its origin during the course of human evolution remains unclear. Here we investigate several markers of early human evolution and their relationship to the genetic risk of schizophrenia. We tested the schizophrenia evolutionary hypothesis by analyzing genome-wide association studies of schizophrenia and other human phenotypes in a statistical framework suited for polygenic architectures. We analyzed evolutionary proxy measures: human accelerated regions, segmental duplications, and ohnologs, representing various time periods of human evolution for overlap with the human genomic loci associated with schizophrenia. Polygenic enrichment plots suggest a higher prevalence of schizophrenia associations in human accelerated regions, segmental duplications and ohnologs. However, the enrichment is mostly accounted for by linkage disequilibrium, especially with functional elements like introns and untranslated regions. Our results did not provide clear evidence that markers of early human evolution are more likely associated with schizophrenia. While SNPs associated with schizophrenia are enriched in HAR, Ohno and SD regions, the enrichment seems to be mediated by affiliation to known genomic enrichment categories. Taken together with previous results, these findings suggest that schizophrenia risk may have mainly developed more recently in human evolution.