Xie Qinglian, Li Zhe, Wang Yan, Zaidi Shan, Baranova Ancha, Zhang Fuquan, Cao Hongbao
Department of Outpatient, West China Hospital of Sichuan University, Chengdu, China.
Mental Health Center and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.
Front Neurol. 2020 Jul 15;11:590. doi: 10.3389/fneur.2020.00590. eCollection 2020.
Preeclampsia (PE) confers a significant risk for subsequent diagnosis with autism spectrum disorder (ASD), with the mechanisms underlying this observation being largely unknown. To identify molecular networks affected by both PE and ASD, we conducted a large-scale literature data mining and a gene set enrichment analysis (GSEA), followed by an expression mega-analysis in 13 independently profiled ASD datasets. Sets of genes implicated in ASD and in PE significantly overlap (156 common genes; = 3.14E), with many biological pathways shared (94 pathways; < 1.00E). A set of PE-driven molecular triggers possibly contributing to worsening the risk of subsequent ASD was identified, possibly representing a regulatory shift toward greater vulnerability to the development of ASD. Mega-analysis of expression highlighted RPS4Y1, an inhibitor of STAT3 that is expressed in a sexually dimorphic manner, as a contributor to both PE and ASD, which should be evaluated as a possible contributor to male predominance in ASD. A set of PE-driven molecular triggers may shift the developing brain toward a greater risk of ASD. One of these triggers, chromosome Y encoded gene RPS4Y1, an inhibitor of STAT3 signaling, warrants evaluation as a possible contributor to male predominance in ASD.
子痫前期（PE）会显著增加后续被诊断为自闭症谱系障碍（ASD）的风险，而这一现象背后的机制在很大程度上尚不清楚。为了确定受PE和ASD共同影响的分子网络，我们进行了大规模的文献数据挖掘和基因集富集分析（GSEA），随后在13个独立分析的ASD数据集中进行了表达元分析。与ASD和PE相关的基因集有显著重叠（156个共同基因；= 3.14E），许多生物学途径也相同（94条途径；< 1.00E）。我们确定了一组可能导致后续ASD风险增加的由PE驱动的分子触发因素，这可能代表了一种向更易患ASD的调节转变。表达元分析突出了RPS4Y1，一种以性别二态性方式表达的STAT3抑制剂，它是PE和ASD的共同影响因素，应作为ASD男性占主导地位的一个可能因素进行评估。一组由PE驱动的分子触发因素可能会使发育中的大脑面临更高的ASD风险。其中一个触发因素，Y染色体编码的基因RPS4Y1，一种STAT3信号传导的抑制剂，值得作为ASD男性占主导地位的一个可能因素进行评估。
