The British Journal of Psychiatry (2007) 190: 200-203. doi: 10.1192/bjp.bp.106.033761
© 2007 The Royal College of Psychiatrists
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SPECIAL ARTICLES

Phenotypic and genetic complexity of psychosis

Invited commentary on ... Schizophrenia: a common disease caused by multiple rare alleles{dagger}

Nick Craddock, PhD, FRCPsych, Michael C. O'Donovan, PhD, FRCPsych and Michael J. Owen, PhD, FRCPsych

Department of Psychological Medicine, Wales School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK

Correspondence: Professor Nick Craddock, Department of Psychological Medicine, Henry Wellcome Building, Wales School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN UK. Email: craddockn{at}cardiff.ac.uk

Declaration of interest None.

{dagger} See pp.194–199, this issue.

Psychosis, like other major psychiatric disorders, is both genetically and clinically complex. Increasingly powerful molecular genetic studies have the potential to identify DNA variation that influences susceptibility to genetically complex disorders. There is a need to use a range of genetic approaches appropriate to identifying a spectrum of risk variants from the common through to the rare. Some variants might have large effects at the level of the individual but most are likely to have modest or small effects at both population and individual level. Extensive clinical heterogeneity is likely to have a significant impact on the power of even the largest studies and, more importantly, will lead to extensive variability between studies and hamper attempts at replication. If we are to realise the potential of molecular genetics, we need to overcome the major limitations imposed by current psychiatric diagnostic classifications and identify clinical phenotypes that reflect the presence of underlying entities with biological validity.


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Schizophrenia: a common disease caused by multiple rare alleles
Jon M. McClellan, Ezra Susser, and Mary-Claire King
BJP 2007 190: 194-199. [Abstract] [Full Text]  



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