In the study—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 work builds upon a recent study that identified 10 risk genes for schizophrenia. However, unlike the current research, the earlier study 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, PhD, a former postdoctoral researcher in the laboratory of Alexander W. Charney, MD, PhD, a co-senior corresponding author of the study and Associate Professor of Psychiatry, Genetics and Genomic Sciences, Neuroscience, and Neurosurgery, 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. That finding raises a question about how we think about brain diseases as a whole, suggested Dr. Charney.
The same variant in the same family may cause autism in one family member and schizophrenia in another.