Brain transcriptional regulatory architecture and schizophrenia etiology converge between East Asian and European ancestral populations

Author:

Liu Sihan,Chen Yu,Wang Feiran,Jiang Yi,Duan Fangyuan,Xia Yan,Ning Zhilin,Li Miao,Qiu Wenying,Ma Chao,Yan Xiao-Xin,Bao Aimin,Dai Jiapei,Kopp Richard F.,Kuney Liz,Huang Jufang,Xu Shuhua,Tang Beisha,Liu Chunyu,Chen ChaoORCID

Abstract

AbstractUnderstanding the genetic architecture of gene expression and splicing in human brain is critical to unlocking the mechanisms of complex neuropsychiatric disorders like schizophrenia (SCZ). Large-scale brain transcriptomic studies are based primarily on populations of European (EUR) ancestry. The uniformity of mono-racial resources may limit important insights into the disease etiology. Here, we characterized brain transcriptional regulatory architecture of East Asians (EAS; n=151), identifying 3,278 expression quantitative trait loci (eQTL) and 4,726 spliceQTL (sQTL). Comparing these to PsychENCODE/BrainGVEX confirmed our hypothesis that the transcriptional regulatory architecture in EAS and EUR brains align. Furthermore, distinctive allelic frequency and linkage disequilibrium impede QTL translation and gene-expression prediction accuracy. Integration of eQTL/sQTL with genome-wide association studies reveals common and novel SCZ risk genes. Pathway-based analyses showing shared SCZ biology point to synaptic and GTPase dysfunction as a prospective pathogenesis. This study elucidates the transcriptional landscape of the EAS brain and emphasizes an essential convergence between EAS and EUR populations.

Publisher

Cold Spring Harbor Laboratory

Reference94 articles.

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