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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)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Chronic Obstructive Pulmonary Disease ; Genetics ; Lung Function ; Polygenic Risk Score; Obstructive Pulmonary-disease; Genome-wide Association; Heritability; Prediction; Spirometry; Phenotypes
ISSN (print) / ISBN 2589-5370
e-ISSN 2589-5370
Zeitschrift EClinicalMedicine
Quellenangaben Band: 75, Heft: , Seiten: , Artikelnummer: 102731 Supplement: ,
Verlag Springer
Verlagsort Radarweg 29, 1043 Nx Amsterdam, Netherlands
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Förderungen Region Stockholm (ALF)
Provincial Government of Gipuzkoa
Basque Department of Health
ERDF
Instituto de Salud Carlos III
Swedish Heart-Lung Foundation
Swedish Research Council
Netherlands Ministry of Health, Welfare, and Sport
Netherlands Ministry of Spatial Planning, Housing
Lung Foun-dation Netherlands
Netherlands Organisation for Scientific Research
Netherlands Organisation for Health Research and Development
Norwegian Institute of Public Health
Central Norway Regional Health Authority
HUNT Research Centre (Faculty of Medicine and Health Sciences at Norwegian University of Science and Technology (NTNU))
Generalitat de Catalunya through the CERCA Program
State Research Agency through the "Centro de Excelencia Severo Ochoa
Spanish Ministry of Science and Innovation
Conselleria de Sanitat Gen-eralitat Valenciana
Netherlands Organisation of Scientific Research NWO Investments
Erasmus MC, Rotterdam, The Netherlands
Municipality of Rotterdam
Ministry for Health, Welfare and Sports, the European Commission (DG XII)
Ministry of Education, Culture, and Science
Research Institute for Diseases in the Elderly (RIDE)
University of Bristol - Erasmus Medical Center and Erasmus Uni-versity, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw)
Wellcome
David Hide Asthma and Allergy Research Trust
Asthma UK
National Institutes of Health USA
UK Medical Research Council
Analysis of Ashford, ALSPAC
Federal Ministry of Education and Research (BMBF)
Genetic Laboratory of the Depart-ment of Internal Medicine, Erasmus MC
Research Institute for Diseases in the Elderly
Spanish Biomedical Research Center in Epidemiology and Public Health (CIBERESP)
Netherlands Genomics Initiative (NGI) /Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA)
Generalitat de Catalunya through the CERCA Program - Ministry of Culture and Science of North Rhine-Westphalia (MKW)