Two newly discovered genes have been linked to schizophrenia, while a previously known gene associated with the risk of schizophrenia has also been linked to autism in a large-scale new study.
Scientists say the findings advance our understanding of brain diseases and could lead to new treatment targets.
Importantly, this is the first known study to look at the risk of schizophrenia in different groups of people, especially those with African ancestry. It revealed that rare deleterious variations in gene proteins increase the risk of schizophrenia in all ethnic groups.
As with many neurological conditions, the exact causes of schizophrenia are varied and complex, and mostly unknown, although it appears that a combination of genetic, environmental, and biological changes in the brain are involved.
“The motivation for this study was to better understand how rare genetic variants influence a person’s risk of developing a serious mental illness, particularly schizophrenia,” says genetic psychiatrist Alexander Charney of the Icahn School of Medicine at Mount Sinai in the US. .
Recent research has shown that people with schizophrenia have more rare protein-degrading variants (PTVs) from a selection of ten genes than people who do not have schizophrenia. PTVs are changes in the DNA code that can cause a gene to produce a protein without essential parts, disrupting its function.
However, that study – like most genetic studies – was conducted on European populations, even though schizophrenia is common worldwide.
In the latest study, two new risk genes, SRRM2 and AKAP11, were identified by comparing the gene sequences of people with schizophrenia with those of healthy people from different groups, particularly those of African descent.
A third gene identified in the study, PCLO, has been linked to schizophrenia in the past, but is now known to increase the risk of autism as well. This adds to what we already know about the genetic overlap between some neurological disorders.
“It is known that there are genetic components that are shared by diseases. Clinically, genes can look different in the same family. The same variant in the same family can cause autism in one family member and schizophrenia in another,” says Charney.
“The idea that the same gene has different manifestations is very interesting to us because it could be helpful when it comes to treating people in the clinic.”
To arrive at their findings, the team performed a meta-analysis involving 35,828 cases and 107,877 controls obtained from previously published datasets.
By pooling data from multiple studies that examined the same phenomenon, a meta-analysis can help researchers identify patterns or inconsistencies in the findings of different studies and provide a more accurate estimate of effect size.
Sequencing the entire genome is costly, so the researchers applied targeted gene sequencing to carefully selected genes from this data — from 11,580 people with a diagnosis of schizophrenia or schizoaffective disorder, and 10,555 people with no known diagnosis of a psychiatric disorder. The people whose genes were included in the study were not closely related and 40 percent were non-European.
“By focusing on a subset of genes, we discovered rare deleterious variants that could potentially lead to new drugs for schizophrenia,” said lead author, geneticist and data analyst Dongjing Liu of the Icahn School of Medicine at Mount Sinai.
“Also important, by studying people from different ancestral backgrounds, we found that rare deleterious variants in evolutionarily constrained genes carry a similar risk of schizophrenia among those different populations and that genetic factors previously identified in predominantly white people are now extended to non-whites. for this debilitating disease.”
Schizophrenia is a serious mental illness that affects thinking, feeling, and behavior. Usually it starts in late adolescence or early adulthood and affects about 7 out of 1,000 people, according to statistics it shortens a person’s life by almost 15 years.
Symptoms include hearing or seeing things that are not there, believing things that are not real, disorganized thinking and behavior, and a lack of motivation. The symptoms can be very upsetting to the person who has them and those around them.
For many people, schizophrenia is manageable with treatment, but current medications don’t work for everyone, symptoms and side effects vary, and more research is needed.
The researchers plan to further investigate the clinical implications of these newly discovered genes on specific symptoms or behaviors of schizophrenia and identify possible drugs to target them.
Liu and colleagues conclude that the main contribution of this study to the field of genetics is that genetic risks are shown to be uniform across ethnic groups.
“Achieving diversity in human genetic research must be a top priority to avoid widening health disparities as genetic research findings are translated into clinical practice,” they write.
This seems like a promising step in the right direction.
The peer-reviewed study has been published in the journal Natural genetics.