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A transcriptome-wide association study implicates specific pre- and post-synaptic abnormalities in schizophrenia.

Lynsey S Hall | Christopher W Medway | Oliver Pain | Antonio F Pardiñas | Elliott G Rees | Valentina Escott-Price | Andrew Pocklington | Nicholas J Bray | Peter A Holmans | James T R Walters | Michael J Owen | Michael C O'Donovan
Human molecular genetics | 2020

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.

Pubmed ID: 31691811

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Associated grants

  • Agency: Medical Research Council, United Kingdom
    Id: MR/L010674/1
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L010674/2
  • Agency: Medical Research Council, United Kingdom
    Id: MR/P005748/1
  • Agency: Medical Research Council, United Kingdom
    Id: G0800509
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L011794/1
  • Agency: NIMH NIH HHS, United States
    Id: U01 MH109514
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L023784/2
  • Agency: Medical Research Council, United Kingdom
    Id: MR/L010305/1

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Reactome (tool)

RRID:SCR_003485

Collection of pathways and pathway annotations. The core unit of the Reactome data model is the reaction. Entities (nucleic acids, proteins, complexes and small molecules) participating in reactions form a network of biological interactions and are grouped into pathways (signaling, innate and acquired immune function, transcriptional regulation, translation, apoptosis and classical intermediary metabolism) . Provides website to navigate pathway knowledge and a suite of data analysis tools to support the pathway-based analysis of complex experimental and computational data sets.

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