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.
Scientists say the findings improve our understanding of brain diseases and could lead to new treatment targets.
Importantly, this is the first known survey to examine the risk of schizophrenia in different groups of people, particularly those of African descent. She found that rare harmful variations in genetic 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 influence a person’s risk of developing serious mental illness, particularly schizophrenia nervosa,” says genetic psychiatrist Alexander Charney of the Icahn School of Medicine in Mount Sinai in the United States.
Recent research has shown that people with schizophrenia have more rare protein truncating variants (PTVs) among a selection of ten genes than people without schizophrenia. PTVs are changes in the DNA code that can cause a gene to produce a protein without essential parts, thereby disrupting its function.
However, this study – like most genetic studies – was conducted on European populations, even though schizophrenia is common around the world.
In the latest investigation, two new risk genes, SRRM2 and AKAP11, were identified through a comparison of the genetic sequences of people with schizophrenia to 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 also increase the risk of autism. This adds to what we already know about the genetic overlap between certain neurological conditions.
“It is known that there are common genetic components to diseases. Clinically, genes can appear different in the same family. The same variant in the same family can cause autism in one family member and schizophrenia in another “, explains Charney.
“The idea that the same gene has different manifestations is of great interest to us, as it could be useful when it comes to treating people in the clinic.”
To arrive at their conclusions, the team conducted a meta-analysis that included 35,828 cases and 107,877 controls obtained from previously published datasets.
By pooling data from multiple studies that have examined the same phenomenon, a meta-analysis can help researchers identify patterns or inconsistencies in the results of different studies and provide a more accurate estimate of the size of the effect.
Whole-genome sequencing is expensive, so the researchers applied targeted gene sequencing to carefully selected genes from these data – from 11,580 people diagnosed with schizophrenia or schizo- and 10,555 people with no known diagnosis of psychiatric disorder. The people whose genes were included in the study were not closely related and 40% were non-European.
“By focusing on a subset of genes, we discovered rare, damaging variants that could potentially lead to new drugs for schizophrenia,” says lead author, geneticist and data analyst Dongjing Liu of the Icahn School of Medicine. Mount Sinai Medicine.
“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.”
Schizophrenia is a serious mental illness that affects thinking, feelings, and behavior. Usually beginning in late adolescence or early adulthood and affecting around 7 in 1,000 people, it shortens a person’s life by nearly 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 for the person who has them and for those around them.
For many people, schizophrenia is well managed 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 potential drugs to target them.
Liu and his colleagues conclude that the main contribution of this study to the field of genetics demonstrates that genetic risk is uniform across ethnicities.
“Achieving diversity in human genetic research must be a top priority to prevent health disparities from widening as the results of genetic research begin to be translated into clinical practice,” they write.
This seems a promising step in the right direction.
The peer-reviewed research has been published in the journal Natural genetics.