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

Huckins, LM; Dobbyn, A; Ruderfer, DM; Hoffman, G; Wang, W; Pardinas, AF; Rajagopal, VM; ... Sullivan, PF; + view all (2019) Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics , 51 (4) pp. 659-674. 10.1038/s41588-019-0364-4. Green open access

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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.

Type: Article
Title: Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41588-019-0364-4
Publisher version: https://doi.org/10.1038/s41588-019-0364-4
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, ACUTE INTERMITTENT PORPHYRIA, COGNITIVE DEFICITS, ASSOCIATION, MOUSE, TRANSCRIPTOME, CHILDHOOD, TRAITS, PSYCHOSIS, DISORDER, VARIANTS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10072226
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