Rights statement: © 2018 Springer Nature Limited. All rights reserved. The Author's Accepted Manuscript (the accepted version of the manuscript as submitted by the author) may only be posted 6 months after the paper is published, consistent with our self-archiving embargo. Please note that the Author’s Accepted Manuscript may not be released under a Creative Commons license. For Nature Research Terms of Reuse of archived manuscripts please see: http://www.nature.com/authors/policies/license.html#terms
Accepted author manuscript, 374 KB, PDF document
Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
<mark>Journal publication date</mark> | 04/2018 |
---|---|
<mark>Journal</mark> | Nature Genetics |
Issue number | 4 |
Volume | 50 |
Number of pages | 11 |
Pages (from-to) | 538-548 |
Publication Status | Published |
Early online date | 9/04/18 |
<mark>Original language</mark> | English |
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 a schizophrenia GWAS of 79,845 individuals from the Psychiatric Genomics Consortium with expression data from brain, blood, and adipose tissues across 3,693 primarily control individuals. We identified 157 TWAS-significant genes, of which 35 did not overlap a known GWAS locus. Of these 157 genes, 42 were associated with specific chromatin features measured in independent samples, thus highlighting potential regulatory targets for follow-up. Suppression of one identified susceptibility gene, mapk3, in zebrafish showed a significant effect on neurodevelopmental phenotypes. Expression and splicing from the brain captured most of the TWAS effect across all genes. This large-scale connection of associations to target genes, tissues, and regulatory features is an essential step in moving toward a mechanistic understanding of GWAS.