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.