Summary: A new study has identified two new genes associated with schizophrenia and a third new gene linked to an increased risk of autism and schizophrenia.
Source: Mount Sinai Health System
Researchers have identified two previously unknown genes linked to schizophrenia and recently implicated a third gene as a risk carrier for both schizophrenia and autism.
Led by the Icahn School of Medicine at Mount Sinai, the multicenter study further demonstrated that the risk of schizophrenia conferred by these rare damaging variants is conserved across ethnicities. The study could also point to new therapies.
The results were published in the March 13 online issue of Natural genetics.
Schizophrenia is one of the most serious mental illnesses. It occurs in about 1 in 100 people and affects the way they think, feel and behave. People with schizophrenia may seem to have lost touch with reality, which can be distressing for them and their families.
In the study – the first known work of its kind to investigate the risk of schizophrenia in various populations, particularly those of African descent – researchers found the two risk genes, SRRM2 And AKAP11, by comparing the genetic sequences of people with schizophrenia to those of healthy controls. The meta-analysis involved existing datasets totaling up to 35,828 cases and 107,877 controls.
The work builds on a recent study that identified 10 risk genes for schizophrenia. However, unlike the current research, the previous study was conducted in people of predominantly white European ancestry.
“By focusing on a subset of genes, we discovered rare, harmful variants that could potentially lead to new drugs for schizophrenia,” said lead author Dongjing Liu, PhD, a former postdoctoral researcher in the lab. Alexander W. Charney, MD, PhD, co-senior corresponding author of the study and associate professor of psychiatry, genetics and genomic sciences, neuroscience and neurosurgery, at Icahn Mount Sinai.
“Also important: By studying people from diverse ancestral backgrounds, we found that rare detrimental variants in evolutionarily limited genes confer a similar magnitude of risk for schizophrenia among these different populations and that previously established genetic factors in people with white predominance have now been extended to non-whites for this debilitating disease.
The third gene reported in the study, PCLO, was previously implicated in schizophrenia, but is now identified as having shared risk for schizophrenia and autism. This finding raises a question about how we think about brain diseases as a whole, Dr. Charney suggested.
“It is known that there are shared genetic components between diseases. Clinically, genes may look different in the same family. The same variant in the same family can cause autism in one family member and schizophrenia in another. The idea that the same gene has different manifestations is very interesting for us, because it could be useful when it comes to treating people in the clinic.
Researchers warn that not all patients have a rare and damaging variant of identified schizophrenia genes. The disease is multifactorial and there is no single factor.
Next, the researchers plan to assess if and how these genes may have a clinical role and may be linked to a specific behavior or symptom of schizophrenia. They will also work to identify drugs that could target the genes under study.
“We wanted to continue the insightful work of my late mentor and Dr. Charney, Pamela Sklar, MD, PhD, psychiatrist, geneticist and neuroscientist whose conceptualization of the study design to first select genes and then study them in a large number of cases and controls was a revolutionary idea,” said Laura M. Huckins, PhD, the study’s co-senior corresponding author, formerly at Icahn Mount Sinai and now associate professor of psychiatry at Yale School of Medicine.
“This work would not have been possible without the tremendous global collaboration and willingness of people to work with us. Our ultimate common goal in the field is to improve the lives of patients, and we are grateful to our associates who have partnered with us in this effort.
The article is titled “The risk of schizophrenia conferred by rare protein-truncating variants is conserved in diverse human populations”.
About this genetics and schizophrenia research news
Author: Karin Eskenazi
Source: Mount Sinai Health System
Contact: Karin Eskenazi – Mount Sinai Health System
Picture: Image is credited to Neuroscience News and was created using DALL-E 2 AI technology
Original research: The findings will appear in Natural genetics