PT  - JOURNAL ARTICLE
AU  - Alexander Gusev
AU  - Nick Mancuso
AU  - Hilary K Finucane
AU  - Yakir Reshef
AU  - Lingyun Song
AU  - Alexias Safi
AU  - Edwin Oh
AU  - Schizophrenia Working Group of the Psychiatric Genomics Consortium
AU  - Steven McCarroll
AU  - Benjamin Neale
AU  - Roel Ophoff
AU  - Michael C O’Donovan
AU  - Nicholas Katsanis
AU  - Gregory E Crawford
AU  - Patrick F Sullivan
AU  - Bogdan Pasaniuc
AU  - Alkes L Price
TI  - Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights
AID  - 10.1101/067355
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 067355
4099  - http://biorxiv.org/content/early/2016/08/02/067355.short
4100  - http://biorxiv.org/content/early/2016/08/02/067355.full
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.