Can a Polygenic Risk Score Predict COPD Early in Life?

Can polygenic risk scores serve as a risk stratification tool for identifying those at high risk for developing COPD at younger ages?

A polygenic risk score (PRS) can predict COPD occurring in patients under the age of 50 years, according to evidence from a recent study published in the European Respiratory Journal.

A high proportion of patients with COPD are currently undiagnosed or initially present with severe disease, losing their chances for early intervention. The use of a PRS could help clinicians individualize risk stratification and preventive measures.

The current study explored whether genetic predisposition to COPD may be linked with early onset of the disorder. Researchers used data from participants in the COPDGene project, an ongoing multicenter study of participants aged 45 to 80 years with a smoking history of at least 10 pack-years at baseline and without severe alpha-1 antitryspsin deficiency, as well as from participants from the Framingham Heart Study, which involved a large population-based cohort with longitudinal spirometry. The current study involved COPDGene project data from 6647 individuals categorized as “non-Hispanic White” (NHW, 52.3% male; n = 6647) and 2464 individuals categorized as “African American” (AA, 57.6% male), as well as data from 6812 individuals from the Framingham Heart Study.

Correctly diagnosed COPD was defined as a self-reported physician diagnosis of COPD or moderate to severe airflow limitation (forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC) <0.7 and FEV1 percent predicted <80%) on baseline post-bronchodilator spirometry. Cox regression was used to investigate the overall and time-dependent effects of a PRS on incident COPD.

The researchers defined COPD occurring before the age of 50 years (COPD50) as “COPD occurring early in life.” Investigators were able to isolate patients in this age group from the COPDGene study to examine the predictive value of the PRS for COPD at younger ages using logistic regression and area-under-the-curve (AUC) analyses with and without other risk factors present in early life, such as childhood asthma.

In Cox models, the PRS showed age-dependent links with incident COPD, including larger effects at younger ages in both cohorts. The PRS was found to be associated with COPD50 (NHW: odds ratio [OR], 1.55; 95% CI, 1.41-1.71. AA: OR, 1.23; 95% CI, 1.05-1.43. FHS: OR, 2.47; 95% CI, 2.12-2.88). In the COPDGene cohort, combining the PRS with known early-life risk factors enhanced prediction of COPD50 in NHW (AUC, 0.69 vs 0.74; P <.0001) and AA participants (AUC, 0.61 vs 0.64; P =.04).

The investigators noted that a potential study limitation was its use of data from studies with 2 different COPD definitions: physician diagnosed vs spirometry defined. The researchers also used age at diagnosis as a proxy for age at onset of COPD, potentially leading to misclassification bias.

Overall, the study findings demonstrate that genetics present a vital means of identifying individuals at high risk for COPD earlier in life, with the PRS offering distinct advantages to affected patients. “A PRS can be calculated using genome-wide genotyping, which can be done once in an individual’s lifetime, is of low cost, and [is] potentially relevant for a large number of diseases. In addition, the performance of the PRS will likely improve with future genetic association studies,” the authors wrote.

Disclosures: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Zhang J, Xu H, Qiao D, et al. A polygenic risk score and age of diagnosis of chronic obstructive pulmonary disease. Eur Respir J. Published online February 3, 2022. doi:10.1183/13993003.01954-2021