Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
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Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. / Huckins, Laura M.; Dobbyn, Amanda; Ruderfer, Douglas M.; Hoffman, Gabriel; Wang, Weiqing; Pardiñas, Antonio F.; Rajagopal, Veera M.; Als, Thomas D.; T. Nguyen, Hoang; Girdhar, Kiran; Boocock, James; Roussos, Panos; Fromer, Menachem; Kramer, Robin; Domenici, Enrico; Gamazon, Eric R.; Purcell, Shaun; CommonMind Consortium; The Schizophrenia Working Group of the PsyUniversity of Copenhagenchiatric Genomics Consortium; iPSYCH-GEMS Schizophrenia Working Group; Johnson, Jessica S.; Shah, Hardik R.; Klein, Lambertus L.; Pers, Tune H.; Hansen, Thomas; Olsen, Line; Rasmussen, Henrik B.; Werge, Thomas; Pedersen, Carsten Bøcker; Nordentoft, Merete; Bækvad-Hansen, Marie; Hansen, Christine Søholm; Daly, Mark J; Sullivan, Patrick F; O'Donovan, Michael C.
I: Nature Genetics, Bind 51, 2019, s. 659-674.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
AU - Huckins, Laura M.
AU - Dobbyn, Amanda
AU - Ruderfer, Douglas M.
AU - Hoffman, Gabriel
AU - Wang, Weiqing
AU - Pardiñas, Antonio F.
AU - Rajagopal, Veera M.
AU - Als, Thomas D.
AU - T. Nguyen, Hoang
AU - Girdhar, Kiran
AU - Boocock, James
AU - Roussos, Panos
AU - Fromer, Menachem
AU - Kramer, Robin
AU - Domenici, Enrico
AU - Gamazon, Eric R.
AU - Purcell, Shaun
AU - CommonMind Consortium
AU - The Schizophrenia Working Group of the PsyUniversity of Copenhagenchiatric Genomics Consortium
AU - iPSYCH-GEMS Schizophrenia Working Group
AU - Johnson, Jessica S.
AU - Shah, Hardik R.
AU - Klein, Lambertus L.
AU - Pers, Tune H.
AU - Hansen, Thomas
AU - Olsen, Line
AU - Rasmussen, Henrik B.
AU - Werge, Thomas
AU - Pedersen, Carsten Bøcker
AU - Nordentoft, Merete
AU - Bækvad-Hansen, Marie
AU - Hansen, Christine Søholm
AU - Daly, Mark J
AU - Sullivan, Patrick F
AU - O'Donovan, Michael C
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1038/s41588-019-0364-4
DO - 10.1038/s41588-019-0364-4
M3 - Journal article
C2 - 30911161
AN - SCOPUS:85063585118
VL - 51
SP - 659
EP - 674
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
ID: 238959486