Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
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Volume
51
Pagination
659 - 674
Publisher
Publisher URL
DOI
10.1038/s41588-019-0364-4
Journal
NATURE GENETICS
Issue
ISSN
1061-4036
Metadata
Show full item recordAbstract
Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.
Authors
Huckins, LM; Dobbyn, A; Ruderfer, DM; Hoffman, G; Wang, W; Pardinas, AF; Rajagopal, VM; Als, TD; Nguyen, HT; Girdhar, KCollections
- Centre for Psychiatry [834]