Li Xiaoyan, Zhao Yiran, Kong Hui, Song Chengcheng, Liu Jie, Xia Junfeng
Information Materials and Intelligent Sensing Laboratory of Anhui Province and Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, China.
iScience. 2023 Sep 19;26(10):107958. doi: 10.1016/j.isci.2023.107958. eCollection 2023 Oct 20.
Alternative splicing (AS) regulation has an essential role in complex diseases. However, the AS profiles in the hippocampal (HIPPO) region of human brain are underexplored. Here, we investigated -acting sQTLs of HIPPO region in 264 samples and identified thousands of significant sQTLs. By enrichment analysis and functional characterization of these sQTLs, we found that the HIPPO sQTLs were enriched among histone-marked regions, transcription factors binding sites, RNA binding proteins sites, and brain disorders-associated loci. Comparative analyses with the dorsolateral prefrontal cortex revealed the importance of AS regulation in HIPPO (r = 0.87). Furthermore, we performed a transcriptome-wide association study of Alzheimer's disease and identified 16 significant genes whose genetically regulated splicing levels may have a causal role in Alzheimer. Overall, our study improves our knowledge of the transcriptome gene regulation in the HIPPO region and provides novel insights into elucidating the pathogenesis of potential genes associated with brain disorders.
可变剪接（AS）调控在复杂疾病中起着至关重要的作用。然而，人类大脑海马体（HIPPO）区域的AS图谱尚未得到充分研究。在此，我们在264个样本中研究了HIPPO区域的顺式作用sQTL，并鉴定出数千个显著的sQTL。通过对这些sQTL的富集分析和功能表征，我们发现HIPPO sQTL在组蛋白标记区域、转录因子结合位点、RNA结合蛋白位点以及与脑部疾病相关的基因座中富集。与背外侧前额叶皮层的比较分析揭示了AS调控在HIPPO中的重要性（r = 0.87）。此外，我们对阿尔茨海默病进行了全转录组关联研究，鉴定出16个显著基因，其基因调控的剪接水平可能在阿尔茨海默病中起因果作用。总体而言，我们的研究增进了我们对HIPPO区域转录组基因调控的了解，并为阐明与脑部疾病相关潜在基因的发病机制提供了新的见解。
