In a groundbreaking study published in Cell Genomics, a team of scientists led by Chris Walsh from the Howard Hughes Medical Institute and Boston Children's Hospital has unveiled intriguing findings about the genetic factors contributing to schizophrenia and introduces a novel avenue for investigating the causes of psychiatric disorders.
The researchers attribute approximately 81% of the liability for schizophrenia to genetic factors, while environmental influences are estimated to account for around 11%, indicating a substantial genetic component at play.
Walsh et al.'s study shifts the focus to type of genetic mutation that has received less attention in the past by examining the non-heritable yet genetic contributions to schizophrenia.
Labeling something as “genetic” is trickier than it might seem. “We originally thought of genetics as the study of inheritance. But now we know that genetic mechanisms go way beyond that,” says Walsh.
As cells divide after fertilization, sometimes an animal-to-be will end up with a different number of a particular gene than normal, which is called a somatic copy-number variant (sCNVs). All the cells derived from the one that made the error will share this copy mutation. As a result, some percentage of the animal's body will carry this mutation, with the derived cells dispersed around the body like a mosaic.
Using a novel filtering method to avoid identifying blood-related sCNVs, the researchers pinpointed potential associations between certain sCNVs and schizophrenia from blood samples. Among the genes exhibiting errors were ABCB11 and NRXN1alpha.
Maury et al. 2023, image open access under the CC BY license 4.0
"With this study, we show that it is possible to find somatic variants in a psychiatric disorder that develops in adulthood," says first author Eduardo A. Maury. Maury,
While these specific sCNVs may be responsible for only a small subset of schizophrenia cases, their discovery “opens up questions about what other disorders might be regulated by these kinds of mutations."