Polygenic risk scores are no better in predicting disease, says study

Scientists from the Icahn School of Medicine at Mount Sinai went through the genetic and medical records of more than 8,000 schizophrenia patients employing advanced computer programs and identified that a tool regularly employed in research for assessing an individual’s genetic risk for a disease, named a polygenic risk score, was not any better in predicting the outcome of a patient’s disease in due course than written reports.

Schizophrenia. Image Credit: Lightspring/Shutterstock.com

The findings put forth crucial questions on the use of polygenic risk scores in real-world, clinical situations, and also indicate that a doctor’s written report might be an unexploited source of predictive information.

Treating schizophrenia patients is a heart-wrenching experience. One of the hardest parts about taking care of patients is trying to determine whether each patient’s condition will worsen or improve. If we could do that, then we might help relieve the suffering that the patients and their loved one’s experience.”

Alexander W. Charney, MD, PhD, Study Senior Author and Assistant Professor, Department of Psychiatry, Icahn School of Medicine at Mount Sinai

Charney is also the assistant professor at the Department of Genetics and Genomic Sciences at Icahn School of Medicine at Mount Sinai.

The research was published in the journal Nature Medicine.

Charney further adds, “Our results show that for the mental illnesses most deeply characterized at the genetic level, the current state of genetics research cannot solve this problem just yet.”

Schizophrenia is a life-shortening mental disorder that changes the way a person acts, thinks, and perceives reality. It affects around 20 million individuals globally. The onset of the symptoms appears in the late teens to early 30s and may last lifelong. Although some patients respond well to treatment, others do not at all.

Even though it is a highly inherited disease, most of the cases are not associated with a single gene. Rather, researchers have identified that the risk of suffering from schizophrenia is impacted by a complex combination of normal genetic variants, neither of which on their own contribute a huge amount to risk. However, they together account for numerous cases. At present around 300 such variants have been linked with schizophrenia.

The polygenic risk score is a regularly employed process for summing up the genetic component of an individual’s risk for a disease. For around 10 years, numerous large research works have demonstrated that the risk scores of schizophrenia patients are considerably greater than that of healthy controls. Equivalent results were seen in research works on other disorders like diabetes and hypertension.

The polygenic risk score basically adds up all of the traits that are associated with a complex disorder. Initially, it was designed to be descriptive tool. More recently, scientists have proposed that it could be an effective tool for precision medicine wherein a person’s genetics is used to diagnose disease and predict outcomes.”

Isotta Landi, PhD, Study Lead Author and Post-Doctoral Fellow, Icahn School of Medicine at Mount Sinai

Landi, who pursues fellowship in Dr. Charney’s laboratory, states, “In this study, we wanted to rigorously test out whether the polygenic risk score could also be a predictive tool.”

The scientists initially compared the genetic and medical records of 762 schizophrenia patients kept in the Mount Sinai Health System’s BioMe™ BioBank program. Particularly, they examined if a patient’s polygenic risk score for schizophrenia can foretell six poor outcomes of each patient any better than the information acquired from the medical reports written by medical practitioners.

To carry out the study, Dr. Landi worked with others to create a state-of-the-art computer program that calculates polygenic risk scores from a patient’s genetic data and applies natural language processing tools to derive information from written reports.

The researchers discovered that two of the outcomes—aggressive behavior and the necessity for hospitalization—were considerably linked with greater polygenic risk scores. However, the scores were not much effective at foretelling these outcomes than the information extracted from the written reports, also joining the two did not alter predictability.

Follow-up experiments supported the findings. For example, the scientists observed no change in the results when they attempted to foretell the outcomes only in individuals with the highest polygenic risk scores.

The researchers ultimately observed the same trend while examining genetic and medical records of 7,779 patients in the Genomic Psychiatry Cohort, a huge National Institutes of Health-funded project. Yet again, the polygenic risk scores did not enhance the capability of clinical data to foretell poor outcomes.

Our results suggest that more work needs to be done to harness the potential that genetics has to improve the treatment of schizophrenia patients. The results also suggest that the detailed medical reports that doctors write may contain much more valuable and predictive information than we originally anticipated.”

Alexander W. Charney, MD, PhD, Study Senior Author and Assistant Professor, Department of Psychiatry, Icahn School of Medicine at Mount Sinai