Genetic Risk Score Supports Diagnosis and Prognosis in Idiopathic Pulmonary Fibrosis

More than 100,000 Americans live with IPF, and an estimated 30,000–40,000 new cases are diagnosed each year, complicating care because symptoms often resemble other interstitial lung diseases. Confirming IPF sometimes requires invasive lung biopsy, heightening the need for noninvasive diagnostic strategies. A new study shows that a genomic risk score can aid diagnosis and identify patients at higher risk of severe outcomes.

Mayo Clinic and Brigham and Women's Hospital co-led an international evaluation of a polygenic risk score (PRS) for IPF in more than 570,000 individuals. Investigators validated a genetic scoring tool designed to help physicians diagnose IPF and stratify risk for severe outcomes, including death or lung transplantation. The study is described as one of the largest real-world assessments of a PRS for IPF.

Researchers calculated a PRS for each participant by combining the effects of more than 60,000 DNA variants associated with IPF. Genomic and electronic health record (EHR) data were drawn from four major biobanks in the U.S. and U.K., including the Mayo Clinic Biobank and Mayo Clinic Tapestry. While each variant confers only a small increment of risk, in aggregate the variants revealed patterns of inherited susceptibility that would otherwise be difficult to detect.

People with high PRS were nearly three times more likely to have IPF than those with lower scores. Predictive performance improved when increasingly specific disease definitions were applied, indicating potential utility in distinguishing IPF from other interstitial lung diseases. Among patients with IPF, those with high genetic risk were 23% more likely to die or require lung transplantation. Findings were published in the American Journal of Respiratory and Critical Care Medicine on July 2, 2026.

Because IPF diagnosis can be delayed, the investigators noted that a noninvasive genetic test using DNA from a blood or saliva sample may help reduce the need for lung biopsy in selected patients. If further validated, they envision genomic risk scores complementing imaging and other diagnostic tools to support more confident clinical decision-making.

“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,” said Victor Ortega, M.D., Ph.D., a pulmonologist, associate director of Mayo Clinic's Center for Individualized Medicine in Arizona, and a co-senior author of the study.

“Most polygenic risk scores are developed in carefully selected research populations. 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,” said Christopher Grilli, Pharm.D., a researcher at Mayo Clinic's Center for Individualized Medicine and co-first author of the study.

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