A study of more than 570,000 people validates a polygenic risk score to identify idiopathic pulmonary fibrosis patients at risk for severe outcomes or death.
RT’s Three Key Takeaways:
- Diagnostic Utility: A polygenic risk score combining more than 60,000 DNA variants was found to be nearly three times more predictive of idiopathic pulmonary fibrosis in high-risk individuals compared to those with lower scores.
- Outcome Prediction: Patients with high genetic risk scores for the disease were 23% more likely to require a lung transplant or face mortality.
- Noninvasive Alternative: Researchers hope this genomic approach will eventually provide a noninvasive alternative to lung biopsies for confirming a diagnosis of idiopathic pulmonary fibrosis.
Mayo Clinic and Brigham and Women’s Hospital researchers have validated a genetic scoring tool that may help physicians diagnose idiopathic pulmonary fibrosis (IPF) and identify patients at risk for severe outcomes, according to a study published in the American Journal of Respiratory and Critical Care Medicine.
The international study analyzed genomic and electronic healthcare record data from more than 570,000 people across four major biobanks in the US and UK. Researchers calculated a polygenic risk score for each participant by combining the effects of more than 60,000 DNA variants associated with IPF. While each variant contributes only a small amount of risk, the researchers noted that together they reveal patterns of inherited susceptibility.
People with high polygenic risk scores were nearly three times more likely to have the disease than those with lower scores, according to the study. The genetic score also became more predictive as researchers applied specific definitions of the disease, suggesting the tool may help distinguish IPF from other forms of interstitial lung disease. Among patients already diagnosed with the disease, those with high genetic risk were 23% more likely to die or require a lung transplant.
“Every patient has a unique genetic blueprint that we can use to estimate risk for the development of disease,” said Victor Ortega, a pulmonologist and associate director of Mayo Clinic’s Center for Individualized Medicine in Arizona. “Polygenic risk scores add a new layer of biological insight into the prediction of pulmonary fibrosis and mortality outcomes, bringing us closer to a future where diagnosis, prognosis, and treatment are informed by each patient’s unique molecular signatures.”
IPF causes irreversible scarring of the lungs that progressively limits a patient’s ability to breathe. More than 100,000 Americans live with the disease, and an estimated 30,000 to 40,000 new cases are diagnosed annually, according to the National Institutes of Health (NIH).
Because symptoms often resemble other interstitial lung diseases, diagnosis is frequently delayed until significant lung damage has occurred. Confirming a diagnosis currently requires an invasive lung biopsy to collect tissue. Researchers hope a noninvasive genetic test using DNA from a blood or saliva sample may reduce the need for those procedures in the future.
“Most polygenic risk scores are developed in carefully selected research populations,” said Christopher Grilli, a researcher at Mayo Clinic’s Center for Individualized Medicine. “Showing that this approach also works across more than half a million people receiving routine clinical care is an important step toward understanding how it can ultimately benefit patients.”
