Identify rare genetic variants associated with the disease in patients with severe schizophrenia
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December 14, 2021. 2:26 pm
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New research shows that examining the genetic mutations in individuals with severe schizophrenia may improve the ability to detect rare genetic variants associated with the disease, according to its authors in the journal ‘PNAS’.
The investigation was carried out at the Irving Medical Center of the Columbia university and was led by Dr. Anthony Zoghbi, now adjunct professor of molecular and human genetics and of psychiatry and behavioral sciences at the Baylor College of Medicine, in United States.
Wide spectrum of symptoms
Patients with schizophrenia have a wide spectrum of observable symptoms. For this study, the researchers focused on the end of that spectrum: a group of 112 patients with severe and extremely resistant schizophrenia who have required prolonged hospitalization in centers in New York State.
Zoghbi and his team examined the mutations of a set of ‘intolerant’ genes, that mutate infrequently in the general healthy population. They carried out genetic sequencing and examined the burden of rare and harmful variants that affect gene function in three groups: people with severe schizophrenia, people with typical schizophrenia, and a control group of healthy individuals.
More than 48% of the individuals with extremely refractory schizophrenia were carriers of at least one of the rare harmful variants, compared with approximately 30% of those with typical schizophrenia and 25% of the control group. The group with severe schizophrenia also had a higher load of gene variants previously associated with schizophrenia than the typical schizophrenia group.
“We believe that this study method could be a new paradigm to try to understand how to enrich a genetic signal in a psychiatric disorder by focusing on individuals who are very severely affected by the disease,” highlights Zoghbi, who is also head of psychiatric genetics at the Baylor Menninger Department of Psychiatry and Behavioral Sciences.
Identifying risk factors for rare variants in individuals with severe schizophrenia could lead to a better understanding of prognosis and resistance to treatment and more opportunities for genetic counseling for families affected by this disease. ‘ Zoghbi says this study may also lay the foundation for future research on therapies targeting the genetic mutations associated with schizophrenia.
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