Identifying Genetic Mutations Can Advance Precision Medicine Efforts

By studying genetic mutations in patients with schizophrenia, researchers can identify disease-associated genetic variants, paving the way for precision medicine.

The research was conducted at Columbia University Irving Medical Center and led by Anthony Zoghbi, MD, now an assistant professor of molecular and human genetics and psychiatry and behavioral sciences at Baylor College of Medicine.

Patients with schizophrenia have a diverse range of observable symptoms. For their study, researchers focused on a group of 112 patients with severe and extremely treatment-resistant schizophrenia who required long-term hospitalization in New York State inpatient facilities.

“The hypothesis is that these patients might have a greater prevalence of disease-causing mutations because they have such a severe form of the illness, and that’s what we ended up seeing,” corresponding author of the study and Beth K. And Stuart C. Yudofsky Scholar at Baylor, Zoghbi, said in a press release.

Zoghbi and the research team examined mutations across a set of “intolerant” genes, which are infrequently mutated in the general, healthy population. The researchers conducted genetic sequencing and examined damaging variants impacting gene function in three groups: people with severe schizophrenia, people with typical schizophrenia, and a control group of healthy individuals.

The data indicated that more than 48 percent of individuals with highly treatment-resistant schizophrenia carried at least one of the damaging variants compared to around 30 percent of individuals with typical schizophrenia and 25 percent of the control group.

Additionally, the severe schizophrenia group has a higher variant burden in genes previously linked to schizophrenia than the group with typical schizophrenia.

“We think that this method of study could be a new paradigm for trying to understand how to enrich a genetic signal in a psychiatric disorder by focusing on individuals who are very severely affected by the disease,” said Zoghbi, who is also the chief of psychiatric genetics in the Menninger Department of Psychiatry and Behavioral Sciences at Baylor.

According to researchers, identifying rare variant risk factors in individuals with serve schizophrenia could lead to a better understanding of the prognosis and provide more opportunities for genetic counseling for families impacted by the disease.

 Additionally, the research could have a significant impact in advancing precision medicine efforts.

“We hope that this research brings light and attention to these patients who are often left out of cutting-edge research because of the severity of their condition,” Zoghbi said.

The study is funded in part by the Chapman Perelman Foundation and the National Institute of Mental Health.