- Title
- Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
- Creator
- Huckins, Laura M.; Buccola, NG; Buckner, RL; Byerley, W; Cahn, W; Cai, G; Campion, D; Cantor, RM; Carr, VJ; Carrera, N; Catts, SV; Chambert, KD; Chan, RCK; Chen, RYL; Chen, EYH; Cheng, W; Cheung, EFC; Chong, SA; Cloninger, CR; Cohen, D; Cohen, N; Cormican, P; Craddock, N; Crowley, JJ; Curtis, D; Davidson, M; Davis, KL; Degenhardt, F; Del Favero, J; Demontis, D; Dikeos, D; Dinan, T; Djurovic, S; Donohoe, G; Drapeau, E; Duan, J; Dudbridge, F; Durmishi, N; Eichhammer, P; Eriksson, J; Dobbyn, Amanda; Boocock, James; Roussos, Panos; Fromer, Menachem; Kramer, Robin; Domenici, Enrico; Gamazon, Eric R.; Purcell, Shaun; Johnson, Jessica S.; Shah, Hardik R.; Klein, Lambertus L.; Ruderfer, Douglas M.; Henskens, Frans A.; Loughland, Carmel M.; Schall, Ulrich; Michie, Patricia T.; Scott, Rodney J.; Gur, RE; Hahn, CG; Schadt, E; Lewis, DA; Haroutunian, V; Hoffman, Gabriel; Peters, MA; Lipska, BK; Buxbaum, JD; Hirai, K; Perumal, TM; Essioux, L; Ripke, S; Neale, BM; Corvin, A; Walters, JTR; Wang, Weiqing; Farh, KH; Holmans, PA; Lee, P; Bulik-Sullivan, B; Collier, DA; Huang, H; Pers, TH; Agartz, I; Agerbo, E; Albus, M; Pardiñas, Antonio F.; Alexander, M; Amin, F; Bacanu, SA; Begemann, M; Belliveau, RA; Bene, J; Henskens, FA; Loughland, CM; Michie, PT; Schall, U; Rajagopal, Veera M.; Scott, RJ; Als, Thomas D.; Nguyen, Hoang T.; Girdhar, Kiran
- Relation
- Nature Genetics Vol. 51, Issue 4, p. 659-674
- Publisher Link
- http://dx.doi.org/10.1038/s41588-019-0364-4
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2019
- Description
- 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.
- Subject
- imputation; gene; schizophrenia; pre and postnatal expression
- Identifier
- http://hdl.handle.net/1959.13/1467233
- Identifier
- uon:47780
- Identifier
- ISSN:1061-4036
- Language
- eng
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