Identification of region-specific splicing QTLs in human hippocampal tissue and its distinctive role in brain disorders

Xiaoyan Li; Yiran Zhao; Hui Kong; Chengcheng Song; Jie Liu; Junfeng Xia

doi:10.1016/j.isci.2023.107958

Identification of region-specific splicing QTLs in human hippocampal tissue and its distinctive role in brain disorders

iScience. 2023 Sep 19;26(10):107958. doi: 10.1016/j.isci.2023.107958. eCollection 2023 Oct 20.

Authors

Xiaoyan Li¹, Yiran Zhao¹, Hui Kong¹, Chengcheng Song¹, Jie Liu¹, Junfeng Xia¹

Affiliation

¹ 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.

Abstract

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 cis-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_g = 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.

Keywords: Genomic analysis; Molecular biology; Molecular mechanism of gene regulation; Neuroscience; Transcriptomics.