Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders.
Characterization of genome-wide association study data reveals spatiotemporal heterogeneity of mental disorders.
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DOI：
10.1186/s12920-020-00832-8
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发表时间：
2020-12-28
影响因子：
2.7
通讯作者：
Jia P
中科院分区：
文献类型：
--
作者：
Dai Y;O'Brien TD;Pei G;Zhao Z;Jia P
精神疾病如精神分裂症（SCZ）、双相情感障碍（BIP）、重度抑郁症（MDD）、注意缺陷多动障碍（ADHD）和自闭症谱系障碍（ASD）通常与大脑发育有关。据报道，这些疾病涉及共同和独特的生物和神经发育过程。在这项工作中，我们开发了一个综合分析框架，以寻求敏感的时空点在大脑发育过程中的每一个障碍。具体来说，我们首先确定了四个大脑区域的时空基因共表达模块三个发育阶段（产前，出生到11岁，13岁以上），共12个时空站点。通过整合GWAS汇总统计和时空共表达模块，我们表征了五种疾病的风险基因及其共表达伴侣。我们发现SCZ与BIP、ASD和ADHD之间有聚集的趋势，并与其他精神疾病保持一定的距离。在基因水平上，我们确定了几个最重要的模块之间共享的基因，如CTNNB 1和LNX 1，以及多个模块中的枢纽基因ATF 2。此外，我们确定了两个时空点在产前阶段的积极表达活动，并强调了一个出生后的点BIP。进一步的功能分析的障碍相关模块突出了ASD和免疫相关的细胞-细胞粘附功能的免疫相关和细胞-细胞粘附的信号通路，分别。我们的研究从网络水平揭示了障碍相关基因的动态变化，揭示了脑发育过程中的时空调控。
Psychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BIP), major depressive disorder (MDD), attention deficit-hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) are often related to brain development. Both shared and unique biological and neurodevelopmental processes have been reported to be involved in these disorders. In this work, we developed an integrative analysis framework to seek for the sensitive spatiotemporal point during brain development underlying each disorder. Specifically, we first identified spatiotemporal gene co-expression modules for four brain regions three developmental stages (prenatal, birth to 11 years old, and older than 13 years), totaling 12 spatiotemporal sites. By integrating GWAS summary statistics and the spatiotemporal co-expression modules, we characterized the risk genes and their co-expression partners for five disorders. We found that SCZ and BIP, ASD and ADHD tend to cluster with each other and keep a distance from other psychiatric disorders. At the gene level, we identified several genes that were shared among the most significant modules, such as CTNNB1 and LNX1, and a hub gene, ATF2, in multiple modules. Moreover, we pinpointed two spatiotemporal points in the prenatal stage with active expression activities and highlighted one postnatal point for BIP. Further functional analysis of the disorder-related module highlighted the apoptotic signaling pathway for ASD and the immune-related and cell-cell adhesion function for SCZ, respectively. Our study demonstrated the dynamic changes of disorder-related genes at the network level, shedding light on the spatiotemporal regulation during brain development.
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影响因子：
14.9
作者：
Jia P;Han G;Zhao J;Lu P;Zhao Z
通讯作者：
Zhao Z
影响因子：
14.9
作者：
Jia, Peilin;Dai, Yulin;Zhao, Zhongming
通讯作者：
Zhao, Zhongming
影响因子：
2.7
作者：
Manuel, Astrid M.;Dai, Yulin;Zhao, Zhongming
通讯作者：
Zhao, Zhongming
影响因子：
120.7
作者：
Castellanos, FX;Lee, PP;Rapoport, JL
通讯作者：
Rapoport, JL
影响因子：
4.5
作者：
Ellison-Wright, Ian;Bullmore, Edward T.
通讯作者：
Bullmore, Edward T.