Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study
Year: 2018
Type: article
Abstract: BACKGROUND: Childhood asthma is strongly influenced by genetics and is a risk factor for reduced lung function and chronic obstructive pulmonary disease (COPD) in adults. This study investigates self-reported childhood asthma in adult smokers from the COPDGene Study. We hypothesize that childhood asthma is associated with decreased lung function, increased risk for COPD, and that a genome-wide association study (GWAS) will show association with established asthma variants. METHODS: We evaluated current and former smokers ages 45-80 of non-Hispanic white (NHW) or African American (AA) race. Childhood asthma was defined by self-report of asthma, diagnosed by a medical professional, with onset at < 16 years or during childhood. Subjects with a history of childhood asthma were compared to those who never had asthma based on lung function, development of COPD, and genetic variation. GWAS was performed in NHW and AA populations, and combined in meta-analysis. Two sets of established asthma SNPs from published literature were examined for association with childhood asthma. RESULTS: ). Among AAs, 339 (12%) had childhood asthma. No SNPs reached genome-wide significance in the AAs or in the meta-analysis combining NHW and AA subjects; however, potential regions of interest were identified. Established asthma SNPs were examined, seven from the NHGRI-EBI database and five with genome-wide significance in the largest pediatric asthma GWAS. Associations were found in the current childhood asthma GWAS with known asthma loci in IL1RL1, IL13, LINC01149, near GSDMB, and in the C11orf30-LRRC32 region (Bonferroni adjusted p < 0.05 for all comparisons). CONCLUSIONS: Childhood asthmatics are at increased risk for COPD. Defining asthma by self-report is valid in populations at risk for COPD, identifying subjects with clinical and genetic characteristics known to associate with childhood asthma. This has potential to improve clinical understanding of asthma-COPD overlap (ACO) and enhance future research into ACO-specific treatment regimens. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).
Source: Respiratory Research
Authors: on behalf of the COPDGene Investigators, Lystra P. Hayden, Michael H. Cho, Benjamin A. Raby, Terri H. Beaty, Edwin K. Silverman, Craig P. Hersh
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,490
Awards: G1651414227, Identifying Genetic Determinants of Severe, Early-Onset COPD, SYSTEMS GENETICS AND GENOMICS OF LUNG DISEASES, G2417563097, INTEGRATIVE GENOMICS OF CLINICAL SUBTYPES IN COPDGENE, Functional Genetics of COPD, (2 of 2) Genetic Epidemiology of COPD, (1 of 2) Genetic Epidemiology of COPD, Genetic Epidemiology of Respiratory Function in Former Preterm Children, SYSTEMS GENOMICS OF THE ASTHMA-COPD OVERLAP SYNDROME, Clinical significance and genetic determinants of novel imaging measures of emphysema distribution in 9,743 smokers, G8643874822, G8819318481, Environmental Health Sciences Research Center, G993448119
OpenAlex ID: W2899487221