RT Journal Article SR Electronic T1 Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights JF bioRxiv FD Cold Spring Harbor Laboratory Press SP 067355 DO 10.1101/067355 A1 Gusev, Alexander A1 Mancuso, Nick A1 Finucane, Hilary K A1 Reshef, Yakir A1 Song, Lingyun A1 Safi, Alexias A1 Oh, Edwin A1 , A1 McCaroll, Steven A1 Neale, Benjamin A1 Ophoff, Roel A1 O'Donovan, Michael C A1 Katsanis, Nicholas A1 Crawford, Gregory E A1 Sullivan, Patrick F A1 Pasaniuc, Bogdan A1 Price, Alkes L YR 2016 UL http://biorxiv.org/content/early/2016/08/02/067355.abstract AB Genome-wide association studies (GWAS) have identified over 100 risk loci for schizophrenia, but the causal mechanisms remain largely unknown. We performed a transcriptome-wide association study (TWAS) integrating expression data from brain, blood, and adipose tissues across 3,693 individuals with schizophrenia GWAS of 79,845 individuals from the Psychiatric Genomics Consortium. We identified 157 genes with a transcriptome-wide significant association, of which 35 did not overlap a known GWAS locus; the largest number involved alternative splicing in brain. 42/157 genes were also associated to specific chromatin phenotypes measured in 121 independent samples (a 4-fold enrichment over background genes). This high-throughput connection of GWAS findings to specific genes, tissues, and regulatory mechanisms is an essential step toward understanding the biology of schizophrenia and moving towards therapeutic interventions.