Natalia Hernandez-Pacheco, Anna Kilanowski, Ashish Kumar, John A Curtin, Núria Olvera, Sara Kress, Xander Bertels, Lies Lahousse, Laxmi Bhatta, Raquel Granell, Sergi Marí, Jose Ramon Bilbao, Yidan Sun, Casper-Emil Tingskov Pedersen, Tarik Karramass, Elisabeth Thiering, Christina Dardani, Simon Kebede Merid, Gang Wang, Jenny Hallberg, Sarah Koch, Judith Garcia-Aymerich, Ana Esplugues, Maties Torrent, Jesus Ibarluzea, Lesley Lowe, Angela Simpson, Ulrike Gehring, Roel C H Vermeulen, Graham Roberts, Anna Bergström, Judith M Vonk, Janine F Felix, Liesbeth Duijts, Klaus Bønnelykke, Nic Timpson, Guy Brusselle, Ben M Brumpton, Arnulf Langhammer, Stephen Turner, John W Holloway, Syed Hasan Arshad, Anhar Ullah, 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
{"title":"探索肺功能气流受限的遗传学--多基因风险评分研究。","authors":"Natalia Hernandez-Pacheco, Anna Kilanowski, Ashish Kumar, John A Curtin, Núria Olvera, Sara Kress, Xander Bertels, Lies Lahousse, Laxmi Bhatta, Raquel Granell, Sergi Marí, Jose Ramon Bilbao, Yidan Sun, Casper-Emil Tingskov Pedersen, Tarik Karramass, Elisabeth Thiering, Christina Dardani, Simon Kebede Merid, Gang Wang, Jenny Hallberg, Sarah Koch, Judith Garcia-Aymerich, Ana Esplugues, Maties Torrent, Jesus Ibarluzea, Lesley Lowe, Angela Simpson, Ulrike Gehring, Roel C H Vermeulen, Graham Roberts, Anna Bergström, Judith M Vonk, Janine F Felix, Liesbeth Duijts, Klaus Bønnelykke, Nic Timpson, Guy Brusselle, Ben M Brumpton, Arnulf Langhammer, Stephen Turner, John W Holloway, Syed Hasan Arshad, Anhar Ullah, 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","doi":"10.1016/j.eclinm.2024.102731","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>A weighted PRS was calculated based on the 82 association signals (<i>p</i> ≤ 5 × 10<sup>-8</sup>) revealed by the largest GWAS of airflow limitation (defined as COPD) to date. This PRS was tested in association with lung function measures (FEV<sub>1</sub>, FVC, and FEV<sub>1</sub>/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.</p><p><strong>Findings: </strong>We found significant associations between the PRS for airflow limitation and: <i>(1)</i> lower pre-bronchodilator FEV<sub>1</sub>/FVC from school age (7-10 years; β: -0.13 z-scores per one PRS z-score increase [-0.15, -0.11], <i>q</i>-value = 7.04 × 10<sup>-53</sup>) to adulthood (41-50 years; β: -0.16 [-0.19, -0.13], <i>q</i>-value = 1.31 × 10<sup>-24</sup>); and <i>(2)</i> lower FEV<sub>1</sub> (from school age: 7-10 years; β: -0.07 [-0.09, -0.05], <i>q</i>-value = 1.65 × 10<sup>-9</sup>, to adulthood: 41-50 years; β: -0.17 [-0.20, -0.13], <i>q</i>-value = 4.48 x 10<sup>-20</sup>). No effect modification by smoking, sex, or a diagnosis of asthma was observed.</p><p><strong>Interpretation: </strong>We provide evidence that a higher genetic risk for COPD is linked to lower lung function from childhood onwards.</p><p><strong>Funding: </strong>This study was supported by CADSET, a Clinical Research Collaboration of the European Respiratory Society.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"75 ","pages":"102731"},"PeriodicalIF":9.6000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577569/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring the genetics of airflow limitation in lung function across the lifespan - a polygenic risk score study.\",\"authors\":\"Natalia Hernandez-Pacheco, Anna Kilanowski, Ashish Kumar, John A Curtin, Núria Olvera, Sara Kress, Xander Bertels, Lies Lahousse, Laxmi Bhatta, Raquel Granell, Sergi Marí, Jose Ramon Bilbao, Yidan Sun, Casper-Emil Tingskov Pedersen, Tarik Karramass, Elisabeth Thiering, Christina Dardani, Simon Kebede Merid, Gang Wang, Jenny Hallberg, Sarah Koch, Judith Garcia-Aymerich, Ana Esplugues, Maties Torrent, Jesus Ibarluzea, Lesley Lowe, Angela Simpson, Ulrike Gehring, Roel C H Vermeulen, Graham Roberts, Anna Bergström, Judith M Vonk, Janine F Felix, Liesbeth Duijts, Klaus Bønnelykke, Nic Timpson, Guy Brusselle, Ben M Brumpton, Arnulf Langhammer, Stephen Turner, John W Holloway, Syed Hasan Arshad, Anhar Ullah, 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\",\"doi\":\"10.1016/j.eclinm.2024.102731\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>A weighted PRS was calculated based on the 82 association signals (<i>p</i> ≤ 5 × 10<sup>-8</sup>) revealed by the largest GWAS of airflow limitation (defined as COPD) to date. This PRS was tested in association with lung function measures (FEV<sub>1</sub>, FVC, and FEV<sub>1</sub>/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.</p><p><strong>Findings: </strong>We found significant associations between the PRS for airflow limitation and: <i>(1)</i> lower pre-bronchodilator FEV<sub>1</sub>/FVC from school age (7-10 years; β: -0.13 z-scores per one PRS z-score increase [-0.15, -0.11], <i>q</i>-value = 7.04 × 10<sup>-53</sup>) to adulthood (41-50 years; β: -0.16 [-0.19, -0.13], <i>q</i>-value = 1.31 × 10<sup>-24</sup>); and <i>(2)</i> lower FEV<sub>1</sub> (from school age: 7-10 years; β: -0.07 [-0.09, -0.05], <i>q</i>-value = 1.65 × 10<sup>-9</sup>, to adulthood: 41-50 years; β: -0.17 [-0.20, -0.13], <i>q</i>-value = 4.48 x 10<sup>-20</sup>). No effect modification by smoking, sex, or a diagnosis of asthma was observed.</p><p><strong>Interpretation: </strong>We provide evidence that a higher genetic risk for COPD is linked to lower lung function from childhood onwards.</p><p><strong>Funding: </strong>This study was supported by CADSET, a Clinical Research Collaboration of the European Respiratory Society.</p>\",\"PeriodicalId\":11393,\"journal\":{\"name\":\"EClinicalMedicine\",\"volume\":\"75 \",\"pages\":\"102731\"},\"PeriodicalIF\":9.6000,\"publicationDate\":\"2024-08-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577569/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EClinicalMedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.eclinm.2024.102731\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EClinicalMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.eclinm.2024.102731","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Exploring the genetics of airflow limitation in lung function across the lifespan - a polygenic risk score study.
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.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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