Medical Dialogues

STUDY IDENTIFIES NEW GENE CARRYING SCHIZOPHRENIA RISK

Researchers have identified two previously unknown genes linked to schizophrenia and newly implicated a third gene as carrying a risk for both schizophrenia and autism. Their study may also point to new therapeutics, it said.
The study, published in the online issue of the Journal Nature Genetics, detailed the two risk genes, SRRM2 and AKAP11, by comparing the gene sequences of people with schizophrenia to those of healthy controls across diverse populations, particularly those of African ancestry.
The meta-analysis involved existing datasets totalling up to 35,828 cases and 107,877 controls, said the study which claimed to be the first known work of its kind studying schizophrenia across ethnicities.
It said that this study was built upon another recent study that identified 10 risk genes for schizophrenia, conducted in people with predominantly white European ancestry. "By focusing on a subset of genes, we discovered variants that could potentially lead to new medicines for schizophrenia," said lead author Dongjing Liu.
"Also significant is that by studying people of various ancestral backgrounds, we found that rare damaging variants in evolutionarily constrained genes confer a similar magnitude of schizophrenia risk among those different populations and that genetic factors previously established in predominantly white people have now been extended to non-whites for this debilitating disease," said Liu.
The third gene flagged in the study, PCLO, was previously implicated in schizophrenia but is now identified as having a shared risk for schizophrenia and autism, the study said.
This finding raises a question about how we think about brain diseases as a whole, suggested Alexander W. Charney, a co-senior corresponding author of the study and associate professor at Icahn Mount Sinai.
"It's been known that there are genetic components shared among illnesses. Clinically, genes could look different in the same family. The same variant in the same family may cause autism in one family member and schizophrenia in another. The idea of the same gene having different manifestations is very interesting to us, as it could be useful when it comes to treating people in the clinic," Charney said.
However, the researchers caution that not every patient has a rare damaging variant in the identified schizophrenia genes. The disease is multifactorial and there is no single factor. The researchers plan to assess whether and how these genes may have a clinical role and may be tied to a specific behavior or symptom of schizophrenia. They will also work to identify drugs that might target the genes in the study.
REFERENCE:
Rammos, A., Kirov, G., Hubbard, L. et al. Family-based analysis of the contribution of rare and common genetic variants to school performance in schizophrenia. Mol Psychiatry (2023). https://doi.org/10.1038/s41380-023-02013-2
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