@article {Gusev067355, author = {Alexander Gusev and Nick Mancuso and Hilary K Finucane and Yakir Reshef and Lingyun Song and Alexias Safi and Edwin Oh and Schizophrenia Working Group of the Psychiatric Genomics Consortium and Steven McCarroll and Benjamin Neale and Roel Ophoff and Michael C O{\textquoteright}Donovan and Nicholas Katsanis and Gregory E Crawford and Patrick F Sullivan and Bogdan Pasaniuc and Alkes L Price}, title = {Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights}, elocation-id = {067355}, year = {2016}, doi = {10.1101/067355}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.}, URL = {https://www.biorxiv.org/content/early/2016/08/02/067355}, eprint = {https://www.biorxiv.org/content/early/2016/08/02/067355.full.pdf}, journal = {bioRxiv} }