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Genetics for Mental Health Disorder

  August, 7 2008 17:11
your information resource in human molecular genetics
Specific human genomic variations associated with schizophrenia are identified by three research groups in Nature and Nature Genetics. Schizophrenia is a severe mental health disorder often characterized by hallucinations, delusions and cognitive deficits. Robust genetic associations with this and other mental disorders have proven difficult to obtain given the complexity of symptoms and environmental effects, so these papers represent a milestone for developing genetic tests.

Two large scientific groups, reporting in Nature, compared the genomes of thousands of unaffected people and patients with schizophrenia for copy number variations (CNVs), which are chunks of more than 100,000 DNA bases that vary between two human genomes. SGENE and partners identified three deletions - one on chromosome 1 and two on chromosome 15 - and demonstrate that these rare variants significantly associate with schizophrenia and related psychoses. The International Schizophrenia Consortium identified two of the same deletions, and also note a greater overall frequency of CNVs in the genome of schizophrenic patients. Both papers also confirm a previously known deletion on chromosome 22, identified in studies with far smaller sample sizes.

In a third paper, in Nature Genetics, Michael O'Donovan and colleagues look at the association of single-nucleotide changes, called SNPs, with schizophrenia. They identify variants at three loci as having strong independent support as risk factors for the disease. The strongest evidence is for a variant near the gene ZNF804A, which encodes a protein that may act to regulate the expression of other genes. The strength of the ZNF804A association increased when individuals with bipolar disorder were included in the analysis, lending support to the notion that schizophrenia and bipolar disorder have some risk factors in common.

Multiple previous studies focused on both SNPs and CNVs associated with schizophrenia, but used a very small sample size. These papers demonstrate a robust and consistent association for at least three genetic loci, and support the hypothesis that disorders like schizophrenia may result from interactions of large stretches of DNA at multiple locations in an individual?s genome.


Kari Stefansson (deCODE Genetics, Reykjavik, Iceland) Author paper [1]
E-mail: kari.stefansson@decode.is

Pamela Sklar (The International Schizophrenia Consortium, Massachusetts General Hospital, Boston, MA, USA) Author paper [2]
E-mail: sklar@chgr.mgh.harvard.edu

Michael O'Donovan (Cardiff University, UK) Author paper [3]
E-mail: odonovanmc@cf.ac.uk

Abstracts available online:

Paper 1.
Paper 2.
Paper 3.

(C) Nature press release.

Message posted by: Trevor M. D'Souza

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