Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Novel findings from CNVs implicate inhibitory and excitatory signaling complexes in schizophrenia

Pocklington, Andrew, Rees, Elliott, Walters, James Tynan Rhys, Han, Jun, Kavanagh, David H., Chambert, Kimberly D., Holmans, Peter Alan, Moran, Jennifer L., McCarroll, Steven A., Kirov, George, O'Donovan, Michael Conlon and Owen, Michael John 2015. Novel findings from CNVs implicate inhibitory and excitatory signaling complexes in schizophrenia. Neuron 86 (5) , pp. 1203-1214. 10.1016/j.neuron.2015.04.022

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB)

Abstract

We sought to obtain novel insights into schizophrenia pathogenesis by exploiting the association between the disorder and chromosomal copy number (CNV) burden. We combined data from 5,745 cases and 10,675 controls with other published datasets containing genome-wide CNV data. In this much-enlarged sample of 11,355 cases and 16,416 controls, we show for the first time that case CNVs are enriched for genes involved in GABAergic neurotransmission. Consistent with non-genetic reports of GABAergic deficits in schizophrenia, our findings now show disrupted GABAergic signaling is of direct causal relevance, rather than a secondary effect or due to confounding. Additionally, we independently replicate and greatly extend previous findings of CNV enrichment among genes involved in glutamatergic signaling. Given the strong functional links between the major inhibitory GABAergic and excitatory glutamatergic systems, our findings converge on a broad, coherent set of pathogenic processes, providing firm foundations for studies aimed at dissecting disease mechanisms.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Medicine
Advanced Research Computing @ Cardiff (ARCCA)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Elsevier (Cell Press)
ISSN: 0896-6273
Funders: MRC
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 16 April 2015
Last Modified: 23 Aug 2019 12:13
URI: http://orca.cf.ac.uk/id/eprint/74080

Citation Data

Cited 54 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics