Researchers analysed whole-genome sequencing data from over 4,600 IPF patients and 400,000 controls across the US and UK. The study focused on rare damaging variants, the well-known MUC5B risk variant, and polygenic risk scores (PRS) for IPF and telomere length. Between 23–43% of patients carried rare variants or exhibited extremely short telomeres, revealing high genetic diversity within IPF.
Role of Telomere Length
Patients with shorter telomere lengths had a higher IPF risk, with polygenic scores showing odds ratios between 1.2–1.6. Notably, telomere-related variants had the strongest impact on patients without rare genetic mutations but with very short telomeres, highlighting their importance in specific subgroups.
Polygenic Risk as a Clinical Tool
Combining clinical features with rare variants, the MUC5B variant, and PRS for IPF and telomere length improved predictive accuracy. In two cohorts, the area under the curve reached nearly 0.9, suggesting that integrating genetic risk could enhance early detection. Telomere length scores alone explained up to 13% of the genetic risk in each dataset.
Implications for Personalized Care
While not yet ready for routine clinical use, polygenic scoring could enable more precise risk stratification, tailored monitoring, and earlier intervention for patients likely to follow a telomere-driven disease course. Experts suggest this approach could help identify IPF endotypes, guiding personalised management of this complex lung disorder.
Looking Ahead
The study underscores the potential of genetic data to refine IPF care strategies. By combining rare and common variant information, including telomere length, clinicians may soon be able to predict disease progression more accurately and offer targeted therapies. Further validation across populations is needed before broad clinical application.