Brain transcriptional regulatory architecture and schizophrenia etiology converge between East Asian and European ancestral populations
Liu, S.; Chen, Y.; Wang, F.; Jiang, Y.; Duan, F.; Xia, Y.; Ning, Z.; Li, M.; Qiu, W.; Ma, C.; Yan, X.; Bao, A.; Dai, J.; Kopp, R. F.; Kuney, L.; Huang, J.; Xu, S.; Tang, B.; Liu, C.; Chen, C.
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Understanding 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.
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