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
SP 067355
DO 10.1101/067355
A1 Alexander Gusev
A1 Nick Mancuso
A1 Hilary K Finucane
A1 Yakir Reshef
A1 Lingyun Song
A1 Alexias Safi
A1 Edwin Oh
A1 Schizophrenia Working Group of the Psychiatric Genomics Consortium
A1 Steven McCarroll
A1 Benjamin Neale
A1 Roel Ophoff
A1 Michael C O’Donovan
A1 Nicholas Katsanis
A1 Gregory E Crawford
A1 Patrick F Sullivan
A1 Bogdan Pasaniuc
A1 Alkes L Price
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.