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Rare genetic variations found in multiplex schizophrenia families

Thursday, 15 March 2018

Scientists at the Centre for Genetic Origins of Health and Disease at UWA and Curtin and the UWA Centre for Clinical Research in Neuropsychiatry have used whole genome sequencing to detect rare genome variations in families with schizophrenia.

Schizophrenia has high heritability, but the genetics of the disease are complex and still not well understood. Over the last decade, studies have indicated that genomic copy number variants (or CNVs, which are deletions or duplications of sections of DNA in the genome) play an important role in the development of schizophrenia. This type of genetic variation poses a greater technical challenge for detection and characterisation when compared to single point mutations in the genome.

In a paper recently published in Schizophrenia Research, the researchers describe their use of data from the Western Australia Family Study of Schizophrenia (WAFSS), which investigates both clinical and genetic aspects of the disease. Genetic analysis of affected multiplex families, in which a person diagnosed with schizophrenia has a 1st- or 2nd-degree relative with the same diagnosis, allows researchers to investigate inherited and new genetic variations that are associated with development of the disease. Analysis of family data also enables better detection of rare genetic variants, as multiple family members may carry the same rare variant, increasing confidence in the results.

Lead author Dr Fayeza Khan said that “by using whole genome sequencing data, which is the most comprehensive genotyping method, and a family-based study design, which allows the same variants to be observed multiple times within families, some of the challenges in studying CNVs have been overcome. Our results have shown that family members with schizophrenia tend to inherit a greater burden of CNVs that affect the coding region of genes, when compared to their unaffected siblings.”

The list of genes found to be affected by CNVs was varied and included several genes with previous implication in neuropsychiatric diseases, including schizophrenia. No single gene or group of genes was over represented in the 91 families, which supports previous evidence about the heterogeneous nature of schizophrenia genetics.

The researchers are continuing to investigate genetic data from the WAFSS to identify other classes of genetic variants, such as point mutations and indels. Combining information from CNVs, point mutations and indels will allow scientists to generate a more comprehensive picture of the genetic variation underlying schizophrenia.

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