An international team of researchers has identified a new gene, CYMA5, which is thought to be associated with schizophrenia. The scientists first conducted a genome-wide association (GWA) analysis on two publicly available datasets, using statistical and bioinformatic prioritisation to uncover the gene. They then verified the association by performing meta-analyses of 23 independent samples.
The study led by Associate Professor Xiangning Chen and Professor Kenneth Kendler at the Virginia Commonwealth University (VCU), Virginia, recognised that individual GWA analyses are not powerful enough to detect the small effects expected in schizophrenia. But that their strength lies in combining the results across studies. The authors suggest that the lack of statistical power of one study on its own, may be one reason for the lack of genetic associations found in schizophrenia.
Professor Chen and colleagues treated the initial GWA analyses as a screen to home in on specific genes that could be followed up. In their initial analysis, they did not apply the conservative statistical cut-offs that are usually used to determine if an association of a genetic marker is significant.
Three markers survived the initial screening and pointed to the CYMA5 gene. The importance of this gene was further highlighted when a bioinformatic search revealed that it had been previously shown to interact with another known candidate gene for schizophrenia, the DTNBP1 gene.
Two of the three SNPs (single nucleotide polymorphisms) in CYMA5 were confirmed in the analysis of the 23 independent samples, following statistical correction. One of the SNPs is particularly promising as it is non-synonymous - a base change that produces a change in the amino acid sequence.
Although the role of the CYMA5 gene in schizophrenia is not yet known, its interaction with the other gene suggests that they are probably involved in the same biological process.
Professor Chen said: 'While its implication for patient care is not clear at this moment, it is fair to say that our paper provides a new target for future research and a practical method to identify other potential risk genes'.
Family, twin, and adoption studies suggest that schizophrenia is heritable. This study, one of the largest association studies of schizophrenia to date, with a combined sample of over 33,000 participants, demonstrates that the multiple genes underlying complex conditions like schizophrenia each have a small effect.
This research was published in the September issue of Molecular Psychiatry.
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