Schizophrenia is known to have a genetic element, and some of the commonly-occurring mutations have been used to power a potential diagnostic. However, the inheritance pattern is complex, and rare coding mutations also play a part. Researchers mining through genetic variants have found that people with schizophrenia carry rather more of these rare mutations than the rest of the population.
According to the WHO, schizophrenia affects around 21 million people worldwide. It is a serious and sometimes disabling mental illness, with serious issues in language, perception and sense of self. It can also include disturbing psychotic symptoms, such as delusions, and visual and auditory hallucinations. It can have a major impact on education, and work and family life.
The team of researchers, from the US, the UK, and the Netherlands, used array-based technology to screen for 250,000 rare variants in 1042 Dutch schizophrenia cases and 961 controls, and found that the people with schizophrenia had more of the mutations than the controls.
“While we cannot point to specific mutations that play a causal role in schizophrenia, we show that schizophrenia patients collectively have more of these mutations than unaffected individuals,” says Loes Olde Loohuis at UCLA’s Center for Neurobehavioral Genetics.
This was confirmed in an independent replication sample of 5585 UK schizophrenia cases and 8103 controls, and the results were published in Nature Communications.
“Even though it’s well-known that schizophrenia has a large genetic component, the specific biological mechanisms at work are not well understood,” says Roel Ophoff at the Center for Neurobehavioral Genetics. “Our research shows that rare coding variants throughout the human genome also contribute to this complex genetic architecture.”
The genes affected by these mutations play a role in foetal brain development, and so these findings support the hypothesis that schizophrenia is a disorder that may originate during the early stages of brain development.
While GenoKey wasn’t involved in this research, the company is working on tools and techniques that allow the mining of complex genetic data sets, for example its work on neuroblastoma risk genotypes.