Researchers have identified two previously unknown genes linked to schizophrenia and newly implicated a third gene as carrying risk for both schizophrenia and autism.
Led by the Icahn School of Medicine at Mount Sinai, the multi-centre study further demonstrated that the schizophrenia risk conferred by these rare damaging variants is conserved across ethnicities.
The study is the first known work of its kind to investigate schizophrenia risk across diverse populations, particularly those of African ancestry.
The investigators found the two risk genes, SRRM2 and AKAP11, by comparing the gene sequences of people with schizophrenia to those of healthy controls. The meta-analysis involved existing datasets totalling up to 35,828 cases and 107,877 controls.
Next, the researchers plan to assess whether and how these genes may have a clinical role and to identify drugs that might target the genes in the study.
Genetic factors
The work builds upon a recent study that identified 10 risk genes for schizophrenia, but which was conducted in people of predominantly white European ancestry.
“By focusing on a subset of genes, we discovered rare damaging variants that could potentially lead to new medicines for schizophrenia,” said lead author Dongjing Liu, a former postdoctoral researcher at Icahn Mount Sinai.
“Also significant: 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.”
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.
Alexander W Charney, a co-senior corresponding author of the study and Associate Professor of Psychiatry, Genetics and Genomic Sciences, Neuroscience, and Neurosurgery, at Icahn Mount Sinai, said: “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.”
