Two newly discovered genes have been linked to schizophrenia, while a previously known gene associated with schizophrenia risk has also been linked to autism in a massive new study.
According to the researchers, the findings increase our understanding of brain diseases and may lead to new treatment targets.
Importantly, this is the first known study to look at the risk of schizophrenia in different groups of people, particularly those of African descent. It revealed that rare deleterious variations in gene proteins increase the risk of schizophrenia in all ethnic groups.
As with many neurological diseases, 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 play a role.
“The motivation for this study was to better understand how rare genetic variants affect a person’s risk of developing serious mental health problems, especially the mental illness schizophrenia,” says genetic psychiatrist Alexander Charney of the Icahn School of Medicine at Mount Sinai in the United States.
Recent studies have shown that people with schizophrenia have more rare protein truncating variants (PTVs) among ten genes than people without schizophrenia. PTVs are DNA code changes that can cause a gene to produce a protein without essential parts, disrupting its function.
However, this study – like most genetic studies – was conducted in 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 the gene sequences of healthy people from different groups, especially those of African descent.
The third gene identified in the study, PCLO, has previously been linked to schizophrenia, but is now known to increase the risk of autism as well. This adds to what we already know about the genetic overlap of some neurological conditions.
“It has been known that there are common genetic components between 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 of the same gene in different manifestations is very interesting to us because it can be useful when treating people in the clinic.”
To arrive at their findings, the team conducted a meta-analysis of 35,828 cases and 107,877 controls obtained from previously published datasets.
By combining data from multiple studies that have investigated the same phenomenon, meta-analysis can help researchers identify patterns or inconsistencies in the results of different studies and provide a more accurate estimate of effect size.
Whole-genome sequencing is expensive, so the researchers applied targeted gene sequencing from this data to carefully selected genes—from 11,580 people diagnosed with schizophrenia or schizoaffective disorder and 10,555 people with no known psychiatric disorder diagnosis. The people whose genes were involved 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,” says lead author Dongjing Liu, a geneticist and data analyst at the Icahn School of Medicine at Mount Sinai.
“Also significant: in studying people with different ancestral backgrounds, we found that rare deleterious variants of evolutionarily restricted genes confer similar risk of schizophrenia in these different populations, and that genetic factors previously entrenched mainly in white people have now been extended to non-whites for this debilitating effect. to illness.”
Schizophrenia is a serious mental illness that affects thinking, feeling, and behavior. It usually starts in late adolescence or early adulthood and affects about 7 out of 1,000 people, and it shortens a person’s life by almost 15 years, according to statistics.
Symptoms include hearing or seeing things that aren’t there, believing things that aren’t real, disorganized thinking and behavior, and lack of motivation. The symptoms can be very upsetting to the person who has them and to those around them.
For many people, schizophrenia is very treatable, but current medications do not work for everyone, symptoms and side effects vary, and more research is needed.
The researchers plan to further investigate the clinical effects of these newly discovered genes on specific schizophrenia symptoms or behaviors and identify potential drugs to target them.
Liu and colleagues conclude that the most important contribution of this study to the field of genetics is that genetic risk is uniform across ethnic groups.
“Achieving diversity in human genetic research must be a priority to prevent worsening health disparities as genetic research results begin to translate 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 Genetics of nature.