ADDING a polygenic risk score (PRS) to conventional case-finding methods improves the identification of undiagnosed chronic obstructive pulmonary disease (COPD), particularly in the general population, new research has shown.
COPD is frequently underdiagnosed, despite its significant impact on morbidity and mortality. While traditional case-finding approaches rely on risk factors and respiratory symptoms, genetic predisposition also plays a role in COPD susceptibility. This study examined whether incorporating a COPD PRS into a case-finding questionnaire enhances the detection of undiagnosed COPD. The research analysed data from the Framingham Heart Study (FHS) and the Genetic Epidemiology of COPD (COPDGene) study, focusing on individuals aged 35 years or older who reported no prior physician-diagnosed COPD.
A cross-sectional analysis was conducted using modified Lung Function Questionnaire (mLFQ) scores and COPD PRS to predict spirometry-defined moderate to severe COPD. The study included 3,385 FHS participants (median age 52.0 years, 45.9% male) and 4,095 COPDGene participants (median age 56.8 years, 55.5% male). Of these, 160 (4.7%) in FHS and 775 (18.9%) in COPDGene met the spirometric criteria for COPD. The addition of PRS to the mLFQ score improved the area under the curve (AUC) from 0.78 to 0.84 (P < .001) in FHS, from 0.69 to 0.72 (P = .04) in non-Hispanic African American COPDGene participants, and from 0.75 to 0.78 (P < .001) in non-Hispanic White COPDGene participants. At a spirometry referral risk threshold of 10%, the PRS improved case reclassification in 13.8% (95% CI, 6.6%-21.0%) of undiagnosed COPD cases in FHS but showed no significant reclassification benefit in COPDGene.
These findings suggest that incorporating genetic risk assessment into COPD case-finding strategies may improve the detection of undiagnosed cases, particularly in the general population. Clinically, this could lead to earlier intervention and targeted spirometry testing, improving patient outcomes. Future studies should explore how PRS-guided screening impacts clinical decision-making and long-term COPD management, including its integration into routine practice to refine case-finding efforts and optimise diagnostic accuracy.
Katrina Thornber, EMJ
Reference
Zhang J et al. Polygenic risk score added to conventional case finding to identify undiagnosed chronic obstructive pulmonary disease. JAMA. 2025.DOI:10.1001/jama.2024.24212.
