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

Author:

Hall Lynsey S1,Medway Christopher W1,Pain Oliver12,Pardiñas Antonio F1,Rees Elliott G1,Escott-Price Valentina1,Pocklington Andrew1,Bray Nicholas J1,Holmans Peter A1,Walters James T R1,Owen Michael J1,O’Donovan Michael C1

Affiliation:

1. MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK

2. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK

Abstract

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.

Funder

Medical Research Council

National Institute of Mental Health

Psychiatric Genomics Consortium

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology,General Medicine

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