TY - JOUR T1 - Developmental and genetic regulation of the human cortex transcriptome in schizophrenia JF - bioRxiv DO - 10.1101/124321 SP - 124321 AU - Andrew E Jaffe AU - Richard E Straub AU - Joo Heon Shin AU - Ran Tao AU - Yuan Gao AU - Leonardo Collado Torres AU - Tony Kam-Thong AU - Hualin S Xi AU - Jie Quan AU - Qiang Chen AU - Carlo Colantuoni AU - Bill Ulrich AU - Brady J. Maher AU - Amy Deep-Soboslay AU - The BrainSeq Consortium AU - Alan Cross AU - Nicholas J. Brandon AU - Jeffrey T Leek AU - Thomas M. Hyde AU - Joel E. Kleinman AU - Daniel R Weinberger Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/05/124321.abstract N2 - GWAS have identified over 108 loci that confer risk for schizophrenia, but risk mechanisms for individual loci are largely unknown. Using developmental, genetic, and illness-based RNA sequencing expression analysis, 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 post-natal life. Within patients and controls, we implemented a novel algorithm for RNA quality adjustment, and identified 237 genes significantly associated with diagnosis that replicated in an independent case-control dataset. These genes implicated synaptic processes and were strongly regulated in early development (p < 10−20). Lastly, we found 42.5% of risk variants associate with nearby genes and diverse transcript features that converge on developmental regulation and subsequent dysregulation in illness and 34 loci show convergent directionality with illness association implicating specific causative transcripts. These data offer new targets for modeling schizophrenia risk in cellular systems. ER -