Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study
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 chil...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12931-018-0890-0 |
| _version_ | 1818263459003891712 |
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| author | Lystra P. Hayden Michael H. Cho Benjamin A. Raby Terri H. Beaty Edwin K. Silverman Craig P. Hersh on behalf of the COPDGene Investigators |
| author_facet | Lystra P. Hayden Michael H. Cho Benjamin A. Raby Terri H. Beaty Edwin K. Silverman Craig P. Hersh on behalf of the COPDGene Investigators |
| author_sort | Lystra P. Hayden |
| collection | DOAJ |
| description | 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 10,199 adult smokers, 730 (7%) reported childhood asthma and 7493 (73%) reported no history of asthma. Childhood asthmatics had reduced lung function and increased risk for COPD (OR 3.42, 95% CI 2.81–4.18). Genotype data was assessed for 8031 subjects. Among NHWs, 391(7%) had childhood asthma, and GWAS identified one genome-wide significant association in KIAA1958 (rs59289606, p = 4.82 × 10− 8). 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). |
| first_indexed | 2024-12-12T19:19:21Z |
| format | Article |
| id | doaj.art-739153d1a3d8455c882f2e5edb001702 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-12T19:19:21Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-739153d1a3d8455c882f2e5edb0017022022-12-22T00:14:39ZengBMCRespiratory Research1465-993X2018-10-0119111110.1186/s12931-018-0890-0Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association studyLystra P. Hayden0Michael H. Cho1Benjamin A. Raby2Terri H. Beaty3Edwin K. Silverman4Craig P. Hersh5on behalf of the COPDGene InvestigatorsDivision of Respiratory Diseases, Boston Children’s HospitalChanning Division of Network Medicine, Brigham and Women’s HospitalDivision of Respiratory Diseases, Boston Children’s HospitalBloomberg School of Public Health, Johns Hopkins UniversityChanning Division of Network Medicine, Brigham and Women’s HospitalChanning Division of Network Medicine, Brigham and Women’s HospitalAbstract 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 10,199 adult smokers, 730 (7%) reported childhood asthma and 7493 (73%) reported no history of asthma. Childhood asthmatics had reduced lung function and increased risk for COPD (OR 3.42, 95% CI 2.81–4.18). Genotype data was assessed for 8031 subjects. Among NHWs, 391(7%) had childhood asthma, and GWAS identified one genome-wide significant association in KIAA1958 (rs59289606, p = 4.82 × 10− 8). 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).http://link.springer.com/article/10.1186/s12931-018-0890-0Childhood asthmaGenome-wide association studyChronic obstructive pulmonary diseaseLung functionGenetic epidemiology |
| spellingShingle | Lystra P. Hayden Michael H. Cho Benjamin A. Raby Terri H. Beaty Edwin K. Silverman Craig P. Hersh on behalf of the COPDGene Investigators Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study Respiratory Research Childhood asthma Genome-wide association study Chronic obstructive pulmonary disease Lung function Genetic epidemiology |
| title | Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study |
| title_full | Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study |
| title_fullStr | Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study |
| title_full_unstemmed | Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study |
| title_short | Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study |
| title_sort | childhood asthma is associated with copd and known asthma variants in copdgene a genome wide association study |
| topic | Childhood asthma Genome-wide association study Chronic obstructive pulmonary disease Lung function Genetic epidemiology |
| url | http://link.springer.com/article/10.1186/s12931-018-0890-0 |
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