Polygenic Risk Score Added to Conventional Case Finding to Identify Undiagnosed Chronic Obstructive Pulmonary Disease

Area of Science:

• Pulmonary Medicine
• Genetics
• Epidemiology

Background:

• Chronic obstructive pulmonary disease (COPD) is frequently undiagnosed.
• Genetic predisposition is a known risk factor for COPD, but its role in early detection is not well-established.

Purpose of the Study:

• To evaluate if a COPD polygenic risk score (PRS) improves the identification of undiagnosed COPD.
• To compare the PRS's effectiveness against a standard case-finding questionnaire (mLFQ) and conventional risk factors.

Main Methods:

• Cross-sectional analysis of data from the Framingham Heart Study (FHS) and COPDGene study.
• Participants (≥35 years) without a prior COPD diagnosis were assessed.
• Logistic models evaluated the predictive performance of mLFQ scores and COPD PRS for spirometry-defined COPD.

Main Results:

• In the FHS cohort, adding COPD PRS to mLFQ significantly improved the prediction of spirometry-defined COPD (AUC increased from 0.78 to 0.84).
• In COPDGene, PRS also improved prediction in non-Hispanic African American (AUC 0.69 to 0.72) and non-Hispanic White participants (AUC 0.75 to 0.78).
• The addition of PRS to mLFQ reclassified 13.8% of undiagnosed COPD cases in FHS at a 10% spirometry referral threshold.

Conclusions:

• A COPD PRS can enhance the identification of undiagnosed COPD beyond traditional case-finding methods.
• The findings suggest genetic risk scores are valuable tools for improving COPD case detection in the general population.
• Further research is warranted to explore the clinical impact of PRS on COPD diagnosis and patient outcomes.