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@article{Hernandez-Pacheco:2024:10.1016/j.eclinm.2024.102731,
author = {Hernandez-Pacheco, N and Kilanowski, A and Kumar, A and Curtin, JA and Olvera, N and Kress, S and Bertels, X and Lahousse, L and Bhatta, L and Granell, R and Marí, S and Bilbao, JR and Sun, Y and Tingskov, Pedersen C-E and Karramass, T and Thiering, E and Dardani, C and Kebede, Merid S and Wang, G and Hallberg, J and Koch, S and Garcia-Aymerich, J and Esplugues, A and Torrent, M and Ibarluzea, J and Lowe, L and Simpson, A and Gehring, U and Vermeulen, RCH and Roberts, G and Bergström, A and Vonk, JM and Felix, JF and Duijts, L and Bønnelykke, K and Timpson, N and Brusselle, G and Brumpton, BM and Langhammer, A and Turner, S and Holloway, JW and Arshad, SH and Ullah, A and Custovic, A and Cullinan, P and Murray, CS and van, den Berge M and Kull, I and Schikowski, T and Wedzicha, JA and Koppelman, G and Faner, R and Agustí, À and Standl, M and Melén, E},
doi = {10.1016/j.eclinm.2024.102731},
journal = {eClinicalMedicine},
title = {Exploring the genetics of airflow limitation in lung function across the lifespan – a polygenic risk score study},
url = {http://dx.doi.org/10.1016/j.eclinm.2024.102731},
volume = {75},
year = {2024}
}
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TY  - JOUR
AB  - BackgroundChronic 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.MethodsA 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.FindingsWe 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.InterpretationWe provide evidence that a higher genetic risk for COPD is linked to lower lung function from childhood onwards.FundingThis study was supported by CADSET, a Clinical Research Collaboration of the European Respiratory Society.
AU  - Hernandez-Pacheco,N
AU  - Kilanowski,A
AU  - Kumar,A
AU  - Curtin,JA
AU  - Olvera,N
AU  - Kress,S
AU  - Bertels,X
AU  - Lahousse,L
AU  - Bhatta,L
AU  - Granell,R
AU  - Marí,S
AU  - Bilbao,JR
AU  - Sun,Y
AU  - Tingskov,Pedersen C-E
AU  - Karramass,T
AU  - Thiering,E
AU  - Dardani,C
AU  - Kebede,Merid S
AU  - Wang,G
AU  - Hallberg,J
AU  - Koch,S
AU  - Garcia-Aymerich,J
AU  - Esplugues,A
AU  - Torrent,M
AU  - Ibarluzea,J
AU  - Lowe,L
AU  - Simpson,A
AU  - Gehring,U
AU  - Vermeulen,RCH
AU  - Roberts,G
AU  - Bergström,A
AU  - Vonk,JM
AU  - Felix,JF
AU  - Duijts,L
AU  - Bønnelykke,K
AU  - Timpson,N
AU  - Brusselle,G
AU  - Brumpton,BM
AU  - Langhammer,A
AU  - Turner,S
AU  - Holloway,JW
AU  - Arshad,SH
AU  - Ullah,A
AU  - Custovic,A
AU  - Cullinan,P
AU  - Murray,CS
AU  - van,den Berge M
AU  - Kull,I
AU  - Schikowski,T
AU  - Wedzicha,JA
AU  - Koppelman,G
AU  - Faner,R
AU  - Agustí,À
AU  - Standl,M
AU  - Melén,E
DO  - 10.1016/j.eclinm.2024.102731
PY  - 2024///
SN  - 2589-5370
TI  - Exploring the genetics of airflow limitation in lung function across the lifespan – a polygenic risk score study
T2  - eClinicalMedicine
UR  - http://dx.doi.org/10.1016/j.eclinm.2024.102731
UR  - https://doi.org/10.1016/j.eclinm.2024.102731
VL  - 75
ER  -
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