A polygenic risk score (PRS) for chronic obstructive pulmonary disease (COPD) is of clinical value in identifying the condition among the general population, research indicates.
Summarizing a person’s COPD genetic risk in this way identified undiagnosed adults and provided added value beyond conventional risk factors and respiratory symptoms, according to the findings in JAMA.
The study demonstrates how combining the effects of numerous genetic variants across the genome into a PRS can improve the ability to predict disease.
“Although the calculation of PRS requires genetic testing, this testing can be done before the onset of symptoms or lung function impairment and only needs to be done once in a person’s lifetime,” reported co-senior author Matthew Moll, MD, from Harvard Medical School, and colleagues.
“The cost of whole-genome genotyping can be $35 or less per person, and these data can be used to inform genetic risks of multiple diseases.”
Up to 70% of people with obstructive lung diseases remain undiagnosed in the U.S. and worldwide, the authors note. Genetic factors contribute substantially to COPD, with its heritability approximately 40% in unrelated individuals.
In a cross-sectional study, Moll et al., examined whether a PRS could improve the identification of adults with undiagnosed moderate-to-severe COPD when combined with a conventional case-finding approach.
To do this, they examined data from 3,385 community-dwelling adults from the Framingham Heart Study (FHS) and 4,095 people who previously or currently smoked from the Genetic Epidemiology of COPD (COPDGene) study. None of the participants reported a physician diagnosis of COPD.
The COPD PRS was developed based on the UK Biobank and SpiroMeta genome-wide association study meta-analysis summary statistics for forced expiratory volume in the first second of expiration (FEV1) and FEV1/forced vital capacity.
A COPD clinical risk score was also calculated using a modified version of the Lung Function Questionnaire (LFQ), which included information on age, smoking history, and the qualitative severity of productive cough, wheezing, and dyspnea on exertion.
Adding the PRS to the modified Lung Function Questionnaire (mLFQ) score significantly improved discrimination in both groups and classification of COPD cases in the FHS.
Adding the PRS to the mLFQ score improved the area under the receiver operating characteristic curve (AUC) from 0.78 to 0.84 for FHS, from 0.69 to 0.72 for COPDGene African-American participants, and from 0.75 to 0.78 for COPDGene White participants.
Using a risk threshold for predicting COPD of 10%, the addition of the PRS to the mLFQ score correctly reclassified 13.8% of participants with COPD in FHS.
By contrast, adding the PRS to the mLFQ score did not reclassify COPD cases in COPDGene, but did correctly reclassify controls as not having COPD.
“The findings suggest that an individual’s genetic risk for COPD, as indicated by a PRS, has a potential added value to conventional case-finding approaches for identifying undiagnosed COPD and guiding referrals for confirmatory spirometry, particularly in community-based settings,” the researchers reported.
“Approximately 5% of adults in the community-based FHS had undiagnosed moderate-to-severe COPD, representing many individuals with undiagnosed COPD in the community.”
