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British Medical Bulletin Advance Access originally published online on May 14, 2009
British Medical Bulletin 2009 91(1):61-74; doi:10.1093/bmb/ldp017
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© The Author 2009. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Schizophrenia genetics: new insights from new approaches

Hywel J. Williams, Michael J. Owen and Michael C. O'Donovan*

MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK

* Correspondence to: Michael C. O'Donovan, MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. E-mail: odonovanmc{at}cf.ac.uk

Introduction: Schizophrenia is a debilitating psychiatric disorder that imposes a considerable burden on sufferers, their families and society. The prominent involvement of genes, combined with the complexity and relative inaccessibility of the brain has led many to suggest that the identification of specific risk loci offers the best chance of understanding pathogenesis.

Sources of data: Recent genome-wide association studies (GWAS) and copy number variation (CNV) publications have been included in this review along with key papers from the fields of schizophrenia, functional psychoses and complex disease mapping.

Areas of agreement: Recent GWAS have now shown that both common alleles of small effect and rare alleles of moderate to large effect contribute to the high heritability of schizophrenia.

Areas of controversy: It is well known that many schizophrenic patients suffer symptoms seen in patients with bipolar disease and vice versa. There is now considerable interest in using aetiologically relevant risk factors, including genes, to explore the validity of the contemporary system of classification.

Growing points: Rare CNVs have been shown to play a role in at least some cases of schizophrenia and it is highly predictable that this figure will rise with the use of technologies with higher resolution or that are better designed to assay common CNVs reliably.

Areas timely for developing research: The findings with common alleles thus far point to overlap in the genetic risk for schizophrenia and bipolar disorder, while the specific CNVs implicated in schizophrenia also increase susceptibility to a range of developmental disorders, including autism, mental retardation, attention deficit-hyperactivity disorder (ADHD) and epilepsy.

Keywords: schizophrenia • genome-wide association study • copy number variation

Accepted for publication April 21, 2009.


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