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What have the genomics ever done for the psychoses?

Published online by Cambridge University Press:  12 October 2009

M. Gill ,
G. Donohoe  and
A. Corvin
M. Gill*
Affiliation:
Neuropsychiatric Genetics Research Group, Department of Psychiatry, School of Medicine, Trinity College Dublin, Ireland
G. Donohoe
Affiliation:
Neuropsychiatric Genetics Research Group, Department of Psychiatry, School of Medicine, Trinity College Dublin, Ireland
A. Corvin
Affiliation:
Neuropsychiatric Genetics Research Group, Department of Psychiatry, School of Medicine, Trinity College Dublin, Ireland
*
*Address for correspondence: Professor M. Gill, Department of Psychiatry, Trinity Center for Health Sciences, St. James' Hospital, Dublin 8, Ireland. (Email: [email protected])
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Abstract

Background

Despite the substantial heritability of the psychoses and their genuine public health burden, the applicability of the genomic approach in psychiatry has been strongly questioned or prematurely dismissed.

Method

A selective review of the recent literature on molecular genetic and genomic approaches to the psychoses including the early output from genome-wide association studies and the genomic analysis of DNA structural variation.

Results

Susceptibility variants at strong candidate genes have been identified including neuregulin, dysbindin, DISC1 and neurexin 1. Rare but highly penetrant copy number variants and new mutations affecting genes involved in neurodevelopment, cell signalling and synaptic function have been described showing some overlapping genetic architecture with other developmental disorders including autism. The de-novo mutations described offer an explanation for the familial sporadic divide and the persistence of schizophrenia in the population. The functional effects of risk variants at the level of cognition and connectivity has been described and recently, ZNF804A has been identified, and the MHC re-identified as risk loci, and it has been shown that at least a third of the variation in liability is due to multiple common risk variants of small effect with a substantial shared genetic liability between schizophrenia and bipolar affective disorder.

Conclusions

The genomics have done much for the psychoses to date and more is anticipated.

Keywords

Copy number variationDNA variantsgeneticspsychosisschizophrenia
Type
Review Article
Information
Psychological Medicine , Volume 40 , Issue 4 , April 2010 , pp. 529 - 540
Copyright
Copyright © Cambridge University Press 2009

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