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Title
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Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
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Author
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Institution/Organisation
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CommonMind Consortium
Psychiat Genomics Consortium
iPSYCH-GEMS Schizophrenia Working
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Nature genetics. - New York, N.Y.
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Publication
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New York, N.Y.
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2019
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ISSN
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1061-4036
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DOI
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10.1038/S41588-019-0364-4
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Volume/pages
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51
:4
(2019)
, p. 659-+
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ISI
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000462767500013
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Pubmed ID
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30911161
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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