Association of a polygenic risk score for chronic obstructive pulmonary disease with lung function across the lifespan
Background: Polygenic Risk Score COPD: Early Life Influences on Lung Function
The concept of the early origins of disease suggests that several mechanisms operate early in life, including the genetics of chronic obstructive pulmonary disease (COPD).
Little is known about this influencing lung function across the lifespan.
Aims: Evaluating the Association of Polygenic Risk Score for COPD with Lung Function Across Ages
- To calculate an individual polygenic risk score (PRS) using gene variants previously linked to COPD;
- To evaluate its association with lung function from childhood to adulthood.
Methods: Calculating Polygenic Risk Score for COPD and Analyzing Lung Function
A PRS was calculated in subjects from 13 population-based studies included in Chronic Airway Diseases Early Stratification (CADSET) based on 82 genetic variants associated with COPD by the largest genome-wide association study to date (35,735 cases/222,076 controls) (Sakornsakolpat et al. Nat Genet 2019;51(3):494-505).
The PRS was then tested for association with lung function at different ages using linear regressions.
Results from each cohort were meta-analyzed by age groups: preschool age, school age, puberty, post-puberty, young adulthood, adulthood, late adulthood, and elderly.
Results: Impact of Polygenic Risk Score on Lung Function from Childhood to Elderly
The association of the PRS with lung function was tested in 44,830 individuals (4-84 years).
It was significantly associated with reduced FEV1/FVC from school ageto elderly.
Associations with reduced FEV1 were also found albeit not consistently with FVC.
There was no major effect modification by age, gender, or smoking.
Conclusions: Strong Links Between Polygenic Risk Score for COPD and Lifelong Lung Function
We found strong associations between a PRS for adult COPD with lung function across ages, suggesting that a higher genetic risk for adult COPD might be linked to poor lung function already since childhood.
Authors
Natalia Hernandez-Pacheco, Anna Kilanowski, Ashish Kumar, John A Curtin, Núria Olvera, Sara Kress, Xanders Bertels, Lies Lahousse, Laxmi Bhatta, Raquel Granell, Sergi Marí, Jose R Bilbao, Yidan Sun, Tarik Karramass, Simon Kebede Merid, Gang Wang, Jenny Hallberg, Maribel Casas, Judith Garcia-Aymerich, Mariona Bustamante, Göran Pershagen, Antonios Georgelis, Lesley Lowe, Angela Simpson, Ulrike Gehring, Roel Ch Vermeulen, Torben Sigsgaard, Vivi Schlünssen, Graham Roberts, Anna Bergström, Judith M Vonk, Janine Felix, Liesbeth Duijts, Nic Timpson, Guy Brusselle, Ben Brumpton, Arnulf Langhammer, Stephen Turner, John W Holloway, Syed Hasan Arshad, Adnan Custovic, Paul Cullinan, Clare S Murray, Maarten Van Den Berge, Inger Kull, Tamara Schikowski, Jadwiga A Wedzicha, Gerard Koppelman, Rosa Faner, Àlvar Agustí, Marie Standl, Erik Melén, O N Behalf Of The Ers Cadset Clinical Research Collaboration
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