Exploring the genetics of airflow limitation in lung function across the lifespan - a polygenic risk score study

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• dc.contributor.author Hernandez-Pacheco, Natalia
• dc.contributor.author Koch, Sarah
• dc.contributor.author García Aymerich, Judith
• dc.contributor.author CADSET
• dc.date.accessioned 2024-11-12T06:36:41Z
• dc.date.available 2024-11-12T06:36:41Z
• dc.date.issued 2024
• dc.description.abstract Background: Chronic obstructive pulmonary disease (COPD) is caused by interactions between many factors across the life course, including genetics. A proportion of COPD may be due to reduced lung growth in childhood. We hypothesized that a polygenic risk score (PRS) for COPD is associated with lower lung function already in childhood and up to adulthood. Methods: A weighted PRS was calculated based on the 82 association signals (p ≤ 5 × 10−8) revealed by the largest GWAS of airflow limitation (defined as COPD) to date. This PRS was tested in association with lung function measures (FEV1, FVC, and FEV1/FVC) in subjects aged 4–50 years from 16 independent cohorts participating in the Chronic Airway Diseases Early Stratification (CADSET) Clinical Research Collaboration. Age-stratified meta-analyses were conducted combining the results from each cohort (n = 45,406). These findings were validated in subjects >50 years old. Findings: We found significant associations between the PRS for airflow limitation and: (1) lower pre-bronchodilator FEV1/FVC from school age (7–10 years; β: −0.13 z-scores per one PRS z-score increase [–0.15, −0.11], q-value = 7.04 × 10−53) to adulthood (41–50 years; β: −0.16 [–0.19, −0.13], q-value = 1.31 × 10−24); and (2) lower FEV1 (from school age: 7–10 years; β: −0.07 [–0.09, −0.05], q-value = 1.65 × 10−9, to adulthood: 41–50 years; β: −0.17 [–0.20, −0.13], q-value = 4.48 x 10−20). No effect modification by smoking, sex, or a diagnosis of asthma was observed. Interpretation: We provide evidence that a higher genetic risk for COPD is linked to lower lung function from childhood onwards. Funding: This study was supported by CADSET, a Clinical Research Collaboration of the European Respiratory Society.
• dc.format.mimetype application/pdf
• dc.identifier.citation Hernandez-Pacheco N, Kilanowski A, Kumar A, Curtin JA, Olvera N, Kress S, et al. Exploring the genetics of airflow limitation in lung function across the lifespan – a polygenic risk score study. eClinicalMedicine. 2024;75:102731. DOI: 10.1016/j.eclinm.2024.102731
• dc.identifier.doi http://dx.doi.org/10.1016/j.eclinm.2024.102731
• dc.identifier.issn 2589-5370
• dc.identifier.uri http://hdl.handle.net/10230/68494
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof eClinicalMedicine. 2024;75:102731
• dc.rights © 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Polygenic risk score
• dc.subject.keyword Genetics
• dc.subject.keyword Chronic obstructive pulmonary disease
• dc.subject.keyword Lung function
• dc.title Exploring the genetics of airflow limitation in lung function across the lifespan - a polygenic risk score study
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion