"De novo" mutations are responsible for over 50% of non-hereditary cases of schizophrenia.
According to a recent study by Columbia Univ. Medical Center researchers, genetic errors that are present in patients but not in their parents (“de novo” mutations) are responsible for over 50% of non-hereditary cases of schizophrenia.
The study, led by Maria Karayiorgou and Joseph Gogos, was performed schizophrenic patients and their families, as well as on a healthy control group; all participants were members of the genetically isolated, European-descent Afrikaner population of South Africa.
The team was inspired to investigate de novo mutations by previous studies performed by Karayiorgou, a professor of psychiatry at Columbia Univ. Medical Center. Over fifteen years ago, Karayiorgou performed a study which described a rare de novo mutation that accounted for 1—2% of sporadic cases of schizophrenia; three years ago, thanks to technological advancements, Columbia researchers were able to identify further de novo mutations responsible for roughly 10% of non-hereditary cases of schizophrenia.
By utilizing state-of-the-art “deep sequencing,” Karayiorgou was able to take this study even further by examining the nucleotide bases of nearly every gene in the human genome. This study yielded the findings of forty mutations, all from different genes and most of them protein-altering.
These results may lead to future discoveries of potentially hundreds of mutations that contribute to the genetics of schizophrenia, which is a vital step in order to comprehend how the disease comes into being.
“Identification of these damaging de novo mutations has fundamentally transformed our understanding of the genetic basis of schizophrenia,” reported first author of the study, Bin Xu, assistant professor of clinical neurobiology at Columbia Univ. Medical Center.
“The fact that the mutations are all from different genes is particularly fascinating,” said Karayiorgou. “It suggests that many more mutations than we suspected may contribute to schizophrenia. This is probably because of the complexity of the neural circuits that are affected by the disease; many genes are needed for their development and function.”
Karayiorgou said that the next step of her research will consist of searching for recurring mutations, as they may supply definitive evidence that a specific mutation contributes to schizophrenia.
Co-author Gogos reported that, by “using innovative neuroscience methods, we hope to identify those neural circuit dysfunctions, so we can target them for drug development.”
While there is still much work left to be done, this study shed some light on two puzzles concerning schizophrenia: one, why the disease preservers, despite the fact that individuals suffering from schizophrenia do not tend to pass on their mutations to their children; and two, why the global incidence rate of the disorder is so high, despite large environmental variations.
The findings were published online in Nature Genetics.