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A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia

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Schizophrenia genetics: advancing on two fronts.

Michael J Owen¹, Hywel J Williams, Michael C O'Donovan

¹MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK. owenmj@cardiff.ac.uk

Current Opinion in Genetics & Development

|April 7, 2009

Summary

Schizophrenia heritability involves common and rare genetic variants. Genome-wide studies highlight copy number variations (CNVs) and specific gene deletions as high-risk factors for schizophrenia.

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Area of Science:

Genetics
Psychiatry
Molecular Biology

Background:

Schizophrenia exhibits high heritability, suggesting a complex genetic architecture.
Genetic studies propose a combination of common, small-effect alleles and rare, large-effect alleles contribute to schizophrenia risk.

Purpose of the Study:

To investigate the genetic underpinnings of schizophrenia, focusing on both common and rare variants.
To identify specific genetic loci and chromosomal abnormalities associated with schizophrenia risk.

Main Methods:

Genome-wide association studies (GWAS) to identify common alleles.
Analysis of copy number variations (CNVs) to detect submicroscopic chromosomal abnormalities.
Examination of specific gene deletions, including NRXN1.

Main Results:

A common allele of small effect was identified at ZNF804a.
An increased burden of CNVs was observed in schizophrenia patients.
Specific deletions at 1q21.1, 15q13.2, and NRXN1 deletions were associated with high schizophrenia risk.

Conclusions:

Schizophrenia genetics are influenced by both common and rare variants.
CNVs, particularly deletions at specific loci like 1q21.1, 15q13.2, and NRXN1, represent significant risk factors for schizophrenia.