A transcriptome-wide association study implicates specific pre- and post-synaptic abnormalities in schizophrenia.
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
01 01 2020
01 01 2020
Historique:
received:
07
05
2019
revised:
31
08
2019
accepted:
02
09
2019
pubmed:
7
11
2019
medline:
22
12
2020
entrez:
7
11
2019
Statut:
ppublish
Résumé
Schizophrenia is a complex highly heritable disorder. Genome-wide association studies (GWAS) have identified multiple loci that influence the risk of developing schizophrenia, although the causal variants driving these associations and their impacts on specific genes are largely unknown. We identify a significant correlation between schizophrenia risk and expression at 89 genes in the dorsolateral prefrontal cortex (P ≤ 9.43 × 10-6), including 20 novel genes. Genes whose expression correlate with schizophrenia were enriched for those involved in abnormal CNS synaptic transmission (PFDR = 0.02) and antigen processing and presentation of peptide antigen via MHC class I (PFDR = 0.02). Within the CNS synaptic transmission set, we identify individual significant candidate genes to which we assign direction of expression changes in schizophrenia. The findings provide strong candidates for experimentally probing the molecular basis of synaptic pathology in schizophrenia.
Identifiants
pubmed: 31691811
pii: 5613686
doi: 10.1093/hmg/ddz253
pmc: PMC7416679
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
159-167Subventions
Organisme : Medical Research Council
ID : MR/L010674/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010674/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P005748/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0800509
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L011794/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH109514
Pays : United States
Organisme : Medical Research Council
ID : MR/L023784/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press.
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