RT Journal Article
SR Electronic
T1 A Polygenic Risk Score and Age of Diagnosis of Chronic Obstructive Pulmonary Disease
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2101954
DO 10.1183/13993003.01954-2021
A1 Jingzhou Zhang
A1 Hanfei Xu
A1 Dandi Qiao
A1 Dawn L. DeMeo
A1 Edwin K. Silverman
A1 George T. O'Connor
A1 Brian D. Hobbs
A1 Josée Dupuis
A1 Michael H. Cho
A1 Matthew Moll
YR 2022
UL http://erj.ersjournals.com/content/early/2022/01/27/13993003.01954-2021.abstract
AB Genetic susceptibility may be associated with earlier onset of chronic obstructive pulmonary disease (COPD). We hypothesised that a polygenic risk score (PRS) for COPD would be associated with earlier age of diagnosis of COPD. In 6647 non-Hispanic white (NHW) and 2464 African American (AA) participants from COPDGene, and 6812 participants from the Framingham Heart Study (FHS), we tested the relationship of the PRS and age of COPD diagnosis. Age at diagnosis was determined by: 1) self-reported age at COPD diagnosis, or 2) age at visits when moderate-to-severe airflow limitation (GOLD 2–4) was observed on spirometry. We used Cox regression to examine the overall and time-dependent effects of the PRS on incident COPD. In the COPDGene study, we also examined the PRS's predictive value for COPD at age<50 years (COPD50) using logistic regression and area-under-the-curve (AUC) analyses, with and without the addition of other risk factors present at early life (e.g., childhood asthma). In Cox models, the PRS demonstrated age-dependent associations with incident COPD, with larger effects at younger ages in both cohorts. The PRS was associated with COPD50 (OR [95% CI]: NHW 1.55 [1.41–1.71], AA 1.23 [1.05–1.43], FHS 2.47 [2.12–2.88]). In COPDGene, adding the PRS to known early-life risk factors improved prediction of COPD50 in NHW (AUC 0.69 versus 0.74, p<0.0001) and AA participants (AUC 0.61 versus 0.64, p=0.04). A COPD polygenic risk score is associated with earlier age of diagnosis of COPD and retains predictive value when added to known early-life risk factors.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Jingzhou Zhang has nothing to disclose.Conflict of interest: Hanfei Xu has nothing to disclose.Conflict of interest: Dandi Qiao has nothing to disclose.Conflict of interest: Dawn L. DeMeo has received support from Bayer and Honoraria from Novartis.Conflict of interest: Edwin K. Silverman received grant support from GlaxoSmithKline and Bayer.Conflict of interest: George T. O'Connor has nothing to disclose.Conflict of interest: Brian D. Hobbs has nothing to disclose.Conflict of interest: Josée Dupuis received NIH funding for salary coverage paid to Boston University.Conflict of interest: Michael H. Cho has received grant support from GlaxoSmithKline and Bayer, consulting fees from Genentech and AstraZeneca, and speaking fees from Illumina.Conflict of interest: Matthew Moll has nothing to disclose.