作者
Andrew E Jaffe, Richard E Straub, Joo Heon Shin, Ran Tao, Yuan Gao, Leonardo Collado-Torres, Tony Kam-Thong, Hualin S Xi, Jie Quan, Qiang Chen, Carlo Colantuoni, William S Ulrich, Brady J Maher, Amy Deep-Soboslay, BrainSeq Consortium, Alan J Cross, Nicholas J Brandon, Jeffrey T Leek, Thomas M Hyde, Joel E Kleinman, Daniel R Weinberger
发表日期
2018/8
期刊
Nature neuroscience
卷号
21
期号
8
页码范围
1117-1125
出版商
Nature Publishing Group US
简介
Genome-wide association studies have identified 108 schizophrenia risk loci, but biological mechanisms for individual loci are largely unknown. Using developmental, genetic and illness-based RNA sequencing expression analysis in human brain, we characterized the human brain transcriptome around these loci and found enrichment for developmentally regulated genes with novel examples of shifting isoform usage across pre- and postnatal life. We found widespread expression quantitative trait loci (eQTLs), including many with transcript specificity and previously unannotated sequence that were independently replicated. We leveraged this general eQTL database to show that 48.1% of risk variants for schizophrenia associate with nearby expression. We lastly found 237 genes significantly differentially expressed between patients and controls, which replicated in an independent dataset, implicated synaptic …
引用总数
20182019202020212022202320247316276586021