精神分裂症遗传风险的动态性在神经发育期间由FOXP1调节的基因内
Deema Ali1,2, Gary Donohoe1,3, Derek W Morris1,2
1Centre for Neuroimaging, Cognition and Genomics (NICOG), University of Galway, University Road, Galway, H91TK33, Ireland.
Human molecular genetics
|December 1, 2025
概括
与FOXP1基因表达相关的精神分裂症 (SCZ) 的遗传风险在神经发育过程中发生动态变化. 儿童早期阶段显示出最强的关联,特别是涉及特定神经元类型的突触功能.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学是一种遗传学.
- 发展生物学 发展生物学
背景情况:
- 叉头盒蛋白P1 (FOXP1) 对神经发育至关重要,并与精神分裂症 (SCZ) 有关.
- 调节FOXP1的基因是SCZ遗传风险的潜在贡献者,因神经发育阶段而有所不同.
研究的目的:
- 研究FOXP1-调节基因在SCZ在产前和产后神经发育中的遗传性中的动态作用.
- 确定特定的发育阶段和细胞群,FOXP1功能障碍对SCZ风险贡献最大.
主要方法:
- 从小鼠和人类模型中分析了多个发育阶段的FOXP1功能丧失的RNA-seq数据.
- 应用链接不平衡得分回归来评估SCZ遗传性丰富性.
- 基因组丰富和SynGO分析将FOXP1目标映射到SCZ相关的基因,突触功能和细胞类型.
主要成果:
- 调节FOXP1的基因在胚胎第14.5天 (E14.5),产后第7天 (P7) 和P47显示了SCZ遗传性的丰富,但不是P0.0.
- 在单细胞研究中,P7基因组对SCZ相关基因表现出最强的丰富.
- 在P7和P47的FOXP1点在突触功能中显著参与,特别是在谷氨酸性神经元中,P47也在GABAergic神经元中表现出丰富.
结论:
- 通过神经发育的动态轨迹,FOXP1调节的基因有助于SCZ遗传风险.
- 与FOXP1点相关的最强遗传风险发生在幼儿时期 (P7),影响突触发育.
- 产前FOXP1点还与突触功能相关联,表明产前早期对SCZ风险的贡献.
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