Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

, CommonMind Consortium and , Schizophrenia Working Group of the Psychiatric Genomics Consorti and , iPSYCH-GEMS Schizophrenia Working Group (2019) Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics, 51 (4). pp. 659-674. ISSN 1061-4036

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Abstract

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.

Item Type:
Journal Article
Journal or Publication Title:
Nature Genetics
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1311
Subjects:
ID Code:
135893
Deposited By:
Deposited On:
06 Aug 2019 13:00
Refereed?:
Yes
Published?:
Published
Last Modified:
25 Oct 2020 06:34