X chromosome associations with chronic obstructive pulmonary disease and related phenotypes: an X chromosome-wide association study.
COPD
Emphysema
Lung function
Sex differences
X chromosome inactivation
X chromosome-wide association study
Journal
Respiratory research
ISSN: 1465-993X
Titre abrégé: Respir Res
Pays: England
ID NLM: 101090633
Informations de publication
Date de publication:
01 Feb 2023
01 Feb 2023
Historique:
received:
21
04
2022
accepted:
18
01
2023
entrez:
2
2
2023
pubmed:
3
2
2023
medline:
4
2
2023
Statut:
epublish
Résumé
The association between genetic variants on the X chromosome to risk of COPD has not been fully explored. We hypothesize that the X chromosome harbors variants important in determining risk of COPD related phenotypes and may drive sex differences in COPD manifestations. Using X chromosome data from three COPD-enriched cohorts of adult smokers, we performed X chromosome specific quality control, imputation, and testing for association with COPD case-control status, lung function, and quantitative emphysema. Analyses were performed among all subjects, then stratified by sex, and subsequently combined in meta-analyses. Among 10,193 subjects of non-Hispanic white or European ancestry, a variant near TMSB4X, rs5979771, reached genome-wide significance for association with lung function measured by FEV This investigation identified loci influencing lung function, COPD, and emphysema in a comprehensive genetic association meta-analysis of X chromosome genetic markers from multiple COPD-related datasets. Sex differences play an important role in the pathobiology of complex lung disease, including X chromosome variants that demonstrate differential effects by sex and variants that may be relevant through escape from X chromosome inactivation. Comprehensive interrogation of the X chromosome to better understand genetic control of COPD and lung function is important to further understanding of disease pathology. Trial registration Genetic Epidemiology of COPD Study (COPDGene) is registered at ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008). Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints Study (ECLIPSE), GlaxoSmithKline study code SCO104960, is registered at ClinicalTrials.gov, NCT00292552 (Active since February 16, 2006). Genetics of COPD in Norway Study (GenKOLS) holds GlaxoSmithKline study code RES11080, Genetics of Chronic Obstructive Lung Disease.
Sections du résumé
BACKGROUND
BACKGROUND
The association between genetic variants on the X chromosome to risk of COPD has not been fully explored. We hypothesize that the X chromosome harbors variants important in determining risk of COPD related phenotypes and may drive sex differences in COPD manifestations.
METHODS
METHODS
Using X chromosome data from three COPD-enriched cohorts of adult smokers, we performed X chromosome specific quality control, imputation, and testing for association with COPD case-control status, lung function, and quantitative emphysema. Analyses were performed among all subjects, then stratified by sex, and subsequently combined in meta-analyses.
RESULTS
RESULTS
Among 10,193 subjects of non-Hispanic white or European ancestry, a variant near TMSB4X, rs5979771, reached genome-wide significance for association with lung function measured by FEV
CONCLUSIONS
CONCLUSIONS
This investigation identified loci influencing lung function, COPD, and emphysema in a comprehensive genetic association meta-analysis of X chromosome genetic markers from multiple COPD-related datasets. Sex differences play an important role in the pathobiology of complex lung disease, including X chromosome variants that demonstrate differential effects by sex and variants that may be relevant through escape from X chromosome inactivation. Comprehensive interrogation of the X chromosome to better understand genetic control of COPD and lung function is important to further understanding of disease pathology. Trial registration Genetic Epidemiology of COPD Study (COPDGene) is registered at ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008). Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints Study (ECLIPSE), GlaxoSmithKline study code SCO104960, is registered at ClinicalTrials.gov, NCT00292552 (Active since February 16, 2006). Genetics of COPD in Norway Study (GenKOLS) holds GlaxoSmithKline study code RES11080, Genetics of Chronic Obstructive Lung Disease.
Identifiants
pubmed: 36726148
doi: 10.1186/s12931-023-02337-1
pii: 10.1186/s12931-023-02337-1
pmc: PMC9891756
doi:
Banques de données
ClinicalTrials.gov
['NCT00608764', 'NCT00292552']
Types de publication
Meta-Analysis
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
38Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL113264
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL089438
Pays : United States
Organisme : NIH HHS
ID : T32HL007427
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089856
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG011393
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL136928
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL114501
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007427
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL089897
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL136851
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA220523
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL105339
Pays : United States
Informations de copyright
© 2023. The Author(s).
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