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Observational Study
. 2018 Oct 29;19(1):209.
doi: 10.1186/s12931-018-0890-0.

Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study

Lystra P Hayden  1   2 , Michael H Cho  3   4 , Benjamin A Raby  5   3   4 , Terri H Beaty  6 , Edwin K Silverman  3   4 , Craig P Hersh  3   4 ; COPDGene Investigators
Collaborators, Affiliations
Observational Study

Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study

Lystra P Hayden et al. Respir Res. .

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).

Keywords: Childhood asthma; Chronic obstructive pulmonary disease; Genetic epidemiology; Genome-wide association study; Lung function.

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Conflict of interest statement

Ethics approval and consent to participate

This study was conducted in accordance with the amended Declaration of Helsinki. This study obtained approval from the Institutional Review Board at Brigham and Women’s Hospital and at each of the twenty-one clinical sites. All participants provided written informed consent for their medical data to be used prior to taking part in the study.

Clinical Center and IRB protocol numbers:

Ann Arbor VA, Ann Arbor, MI (PCC 2008–110732).

Baylor College of Medicine, Houston, TX (H-22209).

Brigham and Women’s Hospital, Boston, MA (2007-P-000554/2; BWH).

Columbia University, New York, NY (IRB-AAAC9324).

Duke University Medical Center, Durham, NC (Pro00004464).

Health Partners Research Foundation, Minneapolis, MN (07–127).

Johns Hopkins University, Baltimore, MD (NA_00011524).

Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, Los Angeles, CA (12756–01).

Michael E. DeBakey VAMC, Houston, TX (H-22202).

Minneapolis VA, Minneapolis, MN (4128-A).

Morehouse School of Medicine, Atlanta, GA (07–1029).

National Jewish Health, Denver, CO (HS-1883a).

Reliant Medical Group, Worcester, MA (1143).

Temple University, Philadelphia, PA (11369).

University of Alabama, Birmingham, AL (FO70712014).

University of California, San Diego, CA (70876).

University of Iowa, Iowa City, IA (200710717).

University of Michigan, Ann Arbor, MI (HUM00014973).

University of Minnesota, Minneapolis, MN (0801 M24949).

University of Pittsburgh, Pittsburgh, PA (PRO07120059).

University of Texas Health Science Center at San Antonio, San Antonio, TX (HSC20070644H).

Competing interests

C.P. Hersh reports personal fees from AstraZeneca, grants from Boehringer Ingelheim, personal fees from Mylan, personal fees from Concert Pharmaceuticals, all of which are outside the submitted work. In the past three years, E.K. Silverman received honoraria from Novartis for Continuing Medical Education Seminars and grant and travel support from GlaxoSmithKline unrelated to this manuscript. M.H. Cho has received grant support from GlaxoSmithKline. Authors L.P. Hayden, B.A. Raby, and T.H. Beaty have no conflicts of interest to disclose.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
LocusZoom Plot of childhood asthma GWAS variants a from non-Hispanic whites in KIAA1958 and b from the meta-analysis in the region near SCHIP1 and its read through transcript IQCJ-SCHIP1
See this image and copyright information in PMC

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