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

Research output: Contribution to journalJournal article

Published
  • CommonMind Consortium
  • Schizophrenia Working Group of the Psychiatric Genomics Consortium
  • iPSYCH-GEMS Schizophrenia Working Group
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<mark>Journal publication date</mark>1/04/2019
<mark>Journal</mark>Nature Genetics
Issue number4
Volume51
Number of pages16
Pages (from-to)659-674
Publication statusPublished
Early online date25/03/19
Original languageEnglish

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.