. 2024 Aug 12:75:102731.

doi: 10.1016/j.eclinm.2024.102731. eCollection 2024 Sep.

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

Natalia Hernandez-Pacheco¹, Anna Kilanowski^{2

3}, Ashish Kumar¹, John A Curtin⁴, Núria Olvera^{5

6}, Sara Kress⁷, Xander Bertels^{8

9}, Lies Lahousse^{8

9}, Laxmi Bhatta^{10

11

12}, Raquel Granell¹³, Sergi Marí¹⁴, Jose Ramon Bilbao^{14

15}, Yidan Sun¹⁶, Casper-Emil Tingskov Pedersen¹⁷, Tarik Karramass^{18

19}, Elisabeth Thiering^{2

3}, Christina Dardani¹³, Simon Kebede Merid¹, Gang Wang^{1

20}, Jenny Hallberg^{1

21}, Sarah Koch^{22

23

24}, Judith Garcia-Aymerich^{22

23

24}, Ana Esplugues^{24

25

26}, Maties Torrent²⁷, Jesus Ibarluzea^{15

28

29

30}, Lesley Lowe⁴, Angela Simpson⁴, Ulrike Gehring³¹, Roel C H Vermeulen³¹, Graham Roberts^{32

33

34}, Anna Bergström^{35

36}, Judith M Vonk^{37

38}, Janine F Felix^{18

39}, Liesbeth Duijts^{18

19}, Klaus Bønnelykke¹⁷, Nic Timpson¹³, Guy Brusselle^{40

41}, Ben M Brumpton^{10

11}, Arnulf Langhammer⁴², Stephen Turner⁴³, John W Holloway^{33

34}, Syed Hasan Arshad^{32

33

44}, Anhar Ullah⁴⁵, Adnan Custovic⁴⁵, Paul Cullinan⁴⁵, Clare S Murray⁴, Maarten van den Berge^{16

38}, Inger Kull¹, Tamara Schikowski⁷, Jadwiga A Wedzicha⁴⁵, Gerard Koppelman^{16

38}, Rosa Faner^{5

6}, Àlvar Agustí^{5

6

46

47}, Marie Standl^{2

48}, Erik Melén^{1

21}; CADSET Clinical Research Collaboration of the European Respiratory Society

Affiliations

¹ Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Sjukhusbacken 10, 118 83, Stockholm, Sweden.
² Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Campus Neuherberg, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
³ Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Center, Lindwurmstraße 4, 80337, Munich, Germany.
⁴ Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust, Cobbett House Manchester Royal Infirmary, Oxford Rd, Manchester, M13 9WL, United Kingdom.
⁵ CIBER de Enfermedades Respiratorias (CIBERES), Spain.
⁶ Universitat de Barcelona, Departament de Biomedicina, Institut D'investigacions Biomediques August Pi I Sunyer (IDIBAPS), Calle Rosselló 149, 08036, Barcelona, Spain.
⁷ IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.
⁸ Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
⁹ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Rotterdam, 3000, CA, the Netherlands.
¹⁰ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Håkon Jarls gt.11, 7491, Trondheim, Norway.
¹¹ HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, S.P. Andersens veg 11, 7031, Trondheim, Norway.
¹² Division of Mental Health Care, St. Olavs Hospital, Trondheim University Hospital, Olav Kyrres gate 9, 7030, Trondheim, Norway.
¹³ Medical Research Council Integrative Epidemiology Unit (MRC-IEU), Population Health Sciences, Bristol Medical School, Faculty of Health Sciences, University of Bristol, 5 Tyndall Ave, Bristol, BS8 1UD, United Kingdom.
¹⁴ Biobizkaia Health Research Institute, University of the Basque Country (UPV/EHU), Leioa, 48940, Bizkaia, Spain.
¹⁵ CIBER Diabetes y Enfermedades Metabólicas asociadas (CIBEDEM), Spain.
¹⁶ University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Department of Pediatric Pulmonology and Pediatric Allergology, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
¹⁷ COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, Ledreborg alle 34, 2820, Gentofte, Denmark.
¹⁸ The Generation R Study Group, Erasmus MC, University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
¹⁹ Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
²⁰ Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, 17 Renmin South Rd Section 3, Wuhou District, Chengdu, Sichuan, 610041, China.
²¹ Sachs' Children and Youth Hospital, Södersjukhuset, Hjalmar Cederströms gata 14, 118 61 Stockholm, Sweden.
²² ISGlobal, Barcelona, Spain.
²³ Universitat Pompeu Fabra, Barcelona, Spain.
²⁴ CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
²⁵ Department of Nursing, University of Valencia, Avenida de Menéndez y Pelayo, 19, 46010 Valencia, Spain.
²⁶ FISABIO-Universitat Jaume I-Universitat de València Joint Research Unit of Epidemiology and Environmental Health, Av. de Catalunya, 21, 46020, Valencia, Spain.
²⁷ Ib-Salut, Area de Salut de Menorca, Palma, Spain.
²⁸ Biodonostia Health Research Institute, Group of Environmental Epidemiology and Child Development, Paseo Doctor Begiristain S/n, 20014, San Sebastian, Spain.
²⁹ Department of Health of the Basque Government, Subdirectorate of Public Health of Gipuzkoa, Avenida Navarra 4, 20013, San Sebastian, Spain.
³⁰ Faculty of Psychology, University of the Basque Country (UPV/EHU), 20008, San Sebastian, Spain.
³¹ Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
³² David Hide Asthma and Allergy Research Centre, St Marys Hospital Nhs Trust, Newport, PO30 5TG, United Kingdom.
³³ NIHR Southampton Biomedical Research Centre, University Hospitals Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, United Kingdom.
³⁴ Human Development and Health, Faculty of Medicine, University of Southampton, 12 University Rd, Southampton, SO17 1BJ, United Kingdom.
³⁵ Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 171 65, Solna, Stockholm, Sweden.
³⁶ Centre for Occupational and Environmental Medicine, Region Stockholm, Torsplan, Solnavägen 4, 113 65, Stockholm, Sweden.
³⁷ Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
³⁸ Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningne, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
³⁹ Department of Pediatrics, Erasmus MC, University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
⁴⁰ Department of Respiratory Medicine, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium.
⁴¹ Departments of Epidemiology and Respiratory Medicine, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Rotterdam, 3000, CA, the Netherlands.
⁴² Department of Levanger Hospital, Nord-Trøndelag Hospital Trust, Helse Nord-Trøndelag, 7601, Levanger, Norway.
⁴³ Royal Aberdeen Children's Hospital NHS Grampian, Westburn Rd, Aberdeen, AB25 2ZG, United Kingdom.
⁴⁴ Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, 12 University Rd, Southampton, SO17 1BJ, United Kingdom.
⁴⁵ National Heart and Lung Institute, Imperial College London, St Mary's Campus Medical School, Norfolk Place, London W2 1PG, United Kingdom.
⁴⁶ Cátedra de Salud Respiratoria, University of Barcelona, Calle Casanovas, 143, 08036, Barcelona, Spain.
⁴⁷ Pulmonary Service, Respiratory Institute, Hospital Clinic, Calle Villarroel, 170, 08036, Barcelona, Spain.
⁴⁸ German Center for Lung Research (DZL), Aulweg 130, 35392, Gießen, Munich, Germany.

PMID: 39568778
PMCID: PMC11577569
DOI: 10.1016/j.eclinm.2024.102731

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

Natalia Hernandez-Pacheco et al. EClinicalMedicine. 2024.

. 2024 Aug 12:75:102731.

doi: 10.1016/j.eclinm.2024.102731. eCollection 2024 Sep.

Authors

Affiliations

¹ Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Sjukhusbacken 10, 118 83, Stockholm, Sweden.
² Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Campus Neuherberg, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
³ Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, University of Munich Medical Center, Lindwurmstraße 4, 80337, Munich, Germany.
⁴ Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester Academic Health Science Centre, and Manchester University NHS Foundation Trust, Cobbett House Manchester Royal Infirmary, Oxford Rd, Manchester, M13 9WL, United Kingdom.
⁵ CIBER de Enfermedades Respiratorias (CIBERES), Spain.
⁶ Universitat de Barcelona, Departament de Biomedicina, Institut D'investigacions Biomediques August Pi I Sunyer (IDIBAPS), Calle Rosselló 149, 08036, Barcelona, Spain.
⁷ IUF - Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.
⁸ Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
⁹ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Rotterdam, 3000, CA, the Netherlands.
¹⁰ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Håkon Jarls gt.11, 7491, Trondheim, Norway.
¹¹ HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU, S.P. Andersens veg 11, 7031, Trondheim, Norway.
¹² Division of Mental Health Care, St. Olavs Hospital, Trondheim University Hospital, Olav Kyrres gate 9, 7030, Trondheim, Norway.
¹³ Medical Research Council Integrative Epidemiology Unit (MRC-IEU), Population Health Sciences, Bristol Medical School, Faculty of Health Sciences, University of Bristol, 5 Tyndall Ave, Bristol, BS8 1UD, United Kingdom.
¹⁴ Biobizkaia Health Research Institute, University of the Basque Country (UPV/EHU), Leioa, 48940, Bizkaia, Spain.
¹⁵ CIBER Diabetes y Enfermedades Metabólicas asociadas (CIBEDEM), Spain.
¹⁶ University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Department of Pediatric Pulmonology and Pediatric Allergology, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
¹⁷ COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, Ledreborg alle 34, 2820, Gentofte, Denmark.
¹⁸ The Generation R Study Group, Erasmus MC, University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
¹⁹ Department of Pediatrics, Division of Respiratory Medicine and Allergology, Erasmus MC, University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
²⁰ Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, 17 Renmin South Rd Section 3, Wuhou District, Chengdu, Sichuan, 610041, China.
²¹ Sachs' Children and Youth Hospital, Södersjukhuset, Hjalmar Cederströms gata 14, 118 61 Stockholm, Sweden.
²² ISGlobal, Barcelona, Spain.
²³ Universitat Pompeu Fabra, Barcelona, Spain.
²⁴ CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
²⁵ Department of Nursing, University of Valencia, Avenida de Menéndez y Pelayo, 19, 46010 Valencia, Spain.
²⁶ FISABIO-Universitat Jaume I-Universitat de València Joint Research Unit of Epidemiology and Environmental Health, Av. de Catalunya, 21, 46020, Valencia, Spain.
²⁷ Ib-Salut, Area de Salut de Menorca, Palma, Spain.
²⁸ Biodonostia Health Research Institute, Group of Environmental Epidemiology and Child Development, Paseo Doctor Begiristain S/n, 20014, San Sebastian, Spain.
²⁹ Department of Health of the Basque Government, Subdirectorate of Public Health of Gipuzkoa, Avenida Navarra 4, 20013, San Sebastian, Spain.
³⁰ Faculty of Psychology, University of the Basque Country (UPV/EHU), 20008, San Sebastian, Spain.
³¹ Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
³² David Hide Asthma and Allergy Research Centre, St Marys Hospital Nhs Trust, Newport, PO30 5TG, United Kingdom.
³³ NIHR Southampton Biomedical Research Centre, University Hospitals Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, United Kingdom.
³⁴ Human Development and Health, Faculty of Medicine, University of Southampton, 12 University Rd, Southampton, SO17 1BJ, United Kingdom.
³⁵ Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, 171 65, Solna, Stockholm, Sweden.
³⁶ Centre for Occupational and Environmental Medicine, Region Stockholm, Torsplan, Solnavägen 4, 113 65, Stockholm, Sweden.
³⁷ Department of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
³⁸ Groningen Research Institute for Asthma and COPD (GRIAC), University of Groningne, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, the Netherlands.
³⁹ Department of Pediatrics, Erasmus MC, University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
⁴⁰ Department of Respiratory Medicine, Ghent University Hospital, Corneel Heymanslaan 10, 9000, Ghent, Belgium.
⁴¹ Departments of Epidemiology and Respiratory Medicine, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Rotterdam, 3000, CA, the Netherlands.
⁴² Department of Levanger Hospital, Nord-Trøndelag Hospital Trust, Helse Nord-Trøndelag, 7601, Levanger, Norway.
⁴³ Royal Aberdeen Children's Hospital NHS Grampian, Westburn Rd, Aberdeen, AB25 2ZG, United Kingdom.
⁴⁴ Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, 12 University Rd, Southampton, SO17 1BJ, United Kingdom.
⁴⁵ National Heart and Lung Institute, Imperial College London, St Mary's Campus Medical School, Norfolk Place, London W2 1PG, United Kingdom.
⁴⁶ Cátedra de Salud Respiratoria, University of Barcelona, Calle Casanovas, 143, 08036, Barcelona, Spain.
⁴⁷ Pulmonary Service, Respiratory Institute, Hospital Clinic, Calle Villarroel, 170, 08036, Barcelona, Spain.
⁴⁸ German Center for Lung Research (DZL), Aulweg 130, 35392, Gießen, Munich, Germany.

PMID: 39568778
PMCID: PMC11577569
DOI: 10.1016/j.eclinm.2024.102731

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.

Keywords: Chronic obstructive pulmonary disease; Genetics; Lung function; Polygenic risk score.

PubMed Disclaimer

Conflict of interest statement

NH-P was supported with a Medium-Term Research Fellowship by the European Academy of Allergy and Clinical Immunology (EAACI) and a Long-Term Research Fellowship by the European Respiratory Society (ERS) (LTRF202101-00861), and lecture honoraria from OMNIPREX, S.L (outside of the submitted work). LLa was supported by the Fund for Scientific Research Flanders (Grant 3G037618), lecture honoraria from IPSA vzw, a non-profit organization facilitating lifelong learning for health care providers, and Chiesi; and consulting fees from AstraZeneca, all paid to the institution. LLa also declares unpaid membership of faculty board and faculty committees of the European Respiratory Society and Belgian Respiratory Society. LB received support from the K.G. Jebsen Center for Genetic Epidemiology funded by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU; The Liaison Committee for Education, Research and Innovation in Central Norway; and the Joint Research Committee between St Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. YS was supported by a grant from the China Scholarship Council. AL declares consulting fees regarding presentation of spirometry from Diagnostica Ltb and lecture honoraria from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline. AC reports research grants funded by MRC, EPSRC, and Wellcome Trust; consulting fees from Worg Pharmaceuticals; lecture honoraria from GlaxoSmithKline, AstraZeneca, Stallergens-Greer, and Sanofi; and unpaid membership of a board of officers of the World Allergy Organization. GK was supported by grants from ZON-MW, Lung Foundation of the Netherlands, UBBO EMMIUS Foundation, GSK, Vertex, European Union (H2020 program), TEVA the Netherlands; consulting fees from AstraZeneca and PURE IMS; lecture fees from AstraZeneca, Boehringer Ingelheim and Sanofi; and participation as a chair at the exquAIro foundation (AI education for medicine and pharma). RF received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. 101044387), Instituto de Salud Carlos III (PI18/00018, PI21/00735), SEPAR and Serra Hunter Program. AA reports research grants, consulting fees, and lecture honoraria by GlaxoSmithKline, AstraZeneca, Menarini, Chiesi, and Sanofi; and unpaid roles as Chair Board of Directors of GOLD and Co-chair of CADSET. MS received funding from ERC under the European Union's Horizon 2020 research and innovation program (grant agreement No. 949906). EM is supported by grants from the EU (ERC, TRIBAL No 757919). EM also declares advisory board and lecture fees from ALK, AstraZeneca, and Chiesi outside the submitted work. The rest of the authors declare no conflicts of interest that might be perceived to influence the interpretation of this article.

Figures

**Fig. 1**
**Flowchart of the methodology used for the calculation of the PRS for airflow limitation and its evaluation with spirometry measurements across the lifespan.** A total of 82 SNPs associated at the genome-wide significance level (p-value ≤5 × 10⁻⁸) by the largest GWAS of COPD susceptibility published to date were initially selected for the PRS estimation in the current study. Several QC procedures were conducted in the base dataset and each of the cohorts that were part of the target dataset. The association between transformed PRS estimates (z-scores) and GLI z-scores of pre-bronchodilator spirometry measurements was assessed through linear regressions at the different available time points per cohort. The association results from each cohort were combined in an age-stratified meta-analysis by age groups from preschool age to adulthood (up to 50 years of age). Validation of these results was conducted in subjects older than 50 years. Moreover, the potential effect of active smoking, sex, and asthma was evaluated through sensitivity analyses. The proportion of lung function variance explained by the PRS was estimated in large sample-sized cohorts across different age groups. 1KGP: 1000 Genomes Project reference panel; CADSET: Chronic Airway Diseases Early Stratification; COPD: chronic obstructive pulmonary disease; GLI: Global Lung Function Initiative; FEV₁: forced respiratory volume in 1 s; FVC: forced vital capacity; GWAS: genome-wide association study; HWE: Hardy–Weinberg equilibrium; INDELs: insertions/deletions; MAF: minor allele frequency; PC: Principal Component of genetic ancestry; PRS: polygenic risk score; QC: quality control; Rsq: imputation quality score; SNP: single nucleotide polymorphism.

**Fig. 2**
**Forest plot of the effect size of the association between the PRS for airflow limitation and spirometry measurements from preschool age to 50-year-old adulthood.** Blue boxes show the association effects in terms of β estimates after meta-analyzing the results from the cohorts included in each age group. The corresponding 95% Confidence Intervals (95% CI) are represented by blue dash lines. The number of cohorts, sample size, effect size, and p-value of the association are also indicated per age group. The q-value represents the adjusted p-value accounting for the false discovery rate. The results shown for the adulthood group including subjects aged between 41 and 50 years correspond to the association results obtained only in HUNT given the absence of more cohorts with available spirometry data within that age range. Results for the age-stratified meta-analysis (random-effects model) are independently shown for each spirometry measurement in terms of z-scores: A) FEV₁/FVC; B) FEV₁; C) FVC. FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity; PRS: polygenic risk score.

**Fig. 3**
**Box plot of variance in FEV**₁**/FVC explained by the PRS for airflow limitation across the lifespan.** The proportion of the total variance in FEV₁/FVC explained by the PRS is shown in the y-axis in terms of R2. The time points from large cohorts from each age group are represented in the x-axis. Boxes are color-coded based on the age group from preschool age to adulthood (>50 years). The median of the R2 is displayed by the thick horizontal line at each box, whereas whiskers extending vertically indicate the minimum and maximum values. The variance explained by the PRS for airflow limitation was estimated including the same sample size and covariates of the basic association model (Principal Components of genetic ancestry and any cohort-specific covariates). FEV₁: forced expiratory volume in 1 s; FVC: forced vital capacity; PRS: polygenic risk score; W1: Genotyping Wave 1; W2: Genotyping Wave 2.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

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