Polygenic Risk Scores, Telomere Length Shape IPF Risk: David Zhang, MD

The role of polygenic risk scores in patients with idiopathic pulmonary fibrosis (IPF) may be influenced by telomere length, according to a recent study published in The Lancet Respiratory Medicine.¹

IPF is an interstitial lung disease with no known origin; however, the recent discovery of how polygenic risk scores and telomere length are associated with patients’ risk of IPF development is a starting point for further research. While the association between telomere length and IPF is not new, the study addressed both rare damaging variants and polygenic risk together to determine whether their presence is causally related to IPF disease progression.

“If we don't find a rare variant, these individuals that have short telomeres, they may still be explained by genetic risk factors, but just a combination of these common variants instead,” the study’s lead author, David Zhang, MD, a pulmonary disease medicine specialist at Columbia University Irving Medical Center, said in an interview with The American Journal of Managed Care^®. “[This study] really highlights that genetic risk is at the forefront…of a lot of these risk factors when it comes to telomere length.”

However, implementing tools to test for polygenic risk scores in a clinical setting presents its own complications.

“The exact cutoffs and how to choose somebody to be higher risk vs low risk is still a difficult challenge, and I think there are a lot more studies that we have to do to decide what is the optimal cutoff,” Zhang explained.

Whereas other diseases may be more strongly associated with polygenic risk scores than IPF, Zhang said the testing comes down to the health care provider’s comfort level performing the test.

“Patients and providers have to be aware and be comfortable with that test and what it means, and also recognize that these tests, like other tests, are part of the puzzle,” Zhang said. “We're not saying that this is the end-all, be-all for predicting somebody's outcome. But we think it can be a good complement to tests that already exist.”

References

1. McCrear S. Telomere length and polygenic risk shape endotypes in idiopathic pulmonary fibrosis. AJMC^®. February 3, 2026. Accessed February 13, 2026. https://www.ajmc.com/view/telomere-length-and-polygenic-risk-shape-endotypes-in-idiopathic-pulmonary-fibrosis