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

CommonMind Consortium, The Schizophrenia Working Group of the PsyUniversity of Copenhagenchiatric Genomics Consortium, iPSYCH-GEMS Schizophrenia Working Group

研究成果: Article

14 引用 (Scopus)

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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.

元の言語English
ページ(範囲)659-674
ページ数16
ジャーナルNature Genetics
51
発行部数4
DOI
出版物ステータスPublished - 01-04-2019

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All Science Journal Classification (ASJC) codes

  • Genetics

これを引用

CommonMind Consortium, The Schizophrenia Working Group of the PsyUniversity of Copenhagenchiatric Genomics Consortium, & iPSYCH-GEMS Schizophrenia Working Group (2019). Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics, 51(4), 659-674. https://doi.org/10.1038/s41588-019-0364-4