A transcriptome-wide association study implicates specific pre- and post-synaptic abnormalities in schizophrenia
Year: 2019
Type: article
Study design: Observational Study
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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddz253
Institutions: Cardiff University, King's College London
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,390
Awards: G1072871761, 5/7 Psychiatric Genomics Consortium: Finding actionable variation, MICA: STRATA - Schizophrenia: Treatment Resistance And Therapeutic Advances, G2936148779, G3056391515, G3921541466, G4548162828, G5318416024, MRC Centre for Neuropsychiatric Genetics and Genomics, G6680420078, Gene regulatory variation in the developing human brain and its role in neuropsychiatric disorders, G7298730862, G8197381132, G8408547947, G8453821592
OpenAlex ID: W2986303961