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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Laura M. Huckins
  • Amanda Dobbyn
  • Douglas M. Ruderfer
  • Gabriel Hoffman
  • Weiqing Wang
  • Antonio F. Pardiñas
  • Veera M. Rajagopal
  • Thomas D. Als
  • Hoang T. Nguyen
  • Kiran Girdhar
  • James Boocock
  • Panos Roussos
  • Menachem Fromer
  • Robin Kramer
  • Enrico Domenici
  • Eric R. Gamazon
  • Shaun Purcell
  • CommonMind Consortium
  • The Schizophrenia Working Group of the PsyUniversity of Copenhagenchiatric Genomics Consortium
  • iPSYCH-GEMS Schizophrenia Working Group
  • Jessica S. Johnson
  • Hardik R. Shah
  • Lambertus L. Klein
  • Tune H. Pers
  • Thomas Hansen
  • Line Olsen
  • Henrik B. Rasmussen
  • Werge, Thomas
  • Carsten Bøcker Pedersen
  • Nordentoft, Merete
  • Marie Bækvad-Hansen
  • Christine Søholm Hansen
  • Mark J Daly
  • Patrick F Sullivan
  • Michael C O'Donovan

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.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind51
Sider (fra-til)659-674
ISSN1061-4036
DOI
StatusUdgivet - 2019

ID: 238959486