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A transcriptome-wide association study implicates specific pre- and post-synaptic abnormalities in schizophrenia
- Source :
- Human Molecular Genetics
- Publication Year :
- 2019
- Publisher :
- Oxford University Press (OUP), 2019.
-
Abstract
- 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.
- Subjects :
- Candidate gene
Quantitative Trait Loci
Genome-wide association study
Biology
Polymorphism, Single Nucleotide
Transcriptome
03 medical and health sciences
0302 clinical medicine
mental disorders
Genetics
medicine
Humans
Genetic Predisposition to Disease
Association Studies Article
Prefrontal cortex
Molecular Biology
Genetics (clinical)
030304 developmental biology
Genetic association
0303 health sciences
Antigen processing
Brain
General Medicine
medicine.disease
Dorsolateral prefrontal cortex
medicine.anatomical_structure
Schizophrenia
Neuroscience
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 14602083 and 09646906
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Human Molecular Genetics
- Accession number :
- edsair.doi.dedup.....36e568584083dd90cf262b3d75a698fa