PuSH - Publikationsserver des Helmholtz Zentrums München

Hernandez-Pacheco, N.* ; Kilanowski, A. ; Kumar, A.* ; Curtin, J.A.* ; Olvera, N.* ; Kress, S.* ; Bertels, X.* ; Lahousse, L.* ; Bhatta, L.* ; Granell, R.* ; Marí, S.* ; Bilbao, J.R.* ; Sun, Y.* ; Tingskov Pedersen, C.E.* ; Karramass, T.* ; Thiering, E. ; Dardani, C.* ; Kebede Merid, S.* ; Wang, G.* ; Hallberg, J.* ; Koch, S.* ; Garcia-Aymerich, J.* ; Esplugues, A.* ; Torrent, M.* ; Ibarluzea, J.* ; Lowe, L.* ; Simpson, A.* ; Gehring, U.* ; Vermeulen, R.C.H.* ; Roberts, G.* ; Bergström, A.* ; Vonk, J.M.* ; Felix, J.F.* ; Duijts, L.* ; Bønnelykke, K.* ; Timpson, N.* ; Brusselle, G.* ; Brumpton, B.M.* ; Langhammer, A.* ; Turner, S.* ; Holloway, J.W.* ; Arshad, S.H.* ; Ullah, A.* ; Custovic, A.* ; Cullinan, P.* ; Murray, C.S.* ; van den Berge, M.* ; Kull, I.* ; Schikowski, T.* ; Wedzicha, J.A.* ; Koppelman, G.* ; Faner, R.* ; Agustí, À.* ; Standl, M. ; Melén, E.*

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

EClinicalMedicine 75:102731 (2024)
Postprint DOI PMC
Open Access Gold
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.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Chronic Obstructive Pulmonary Disease ; Genetics ; Lung Function ; Polygenic Risk Score
ISSN (print) / ISBN 2589-5370
e-ISSN 2589-5370
Zeitschrift EClinicalMedicine
Quellenangaben Band: 75, Heft: , Seiten: , Artikelnummer: 102731 Supplement: ,
Verlag Springer
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)