A genome-wide association study of bronchodilator response in asthmatics

Q. L. Duan, J. Lasky-Su, B. E. Himes, W. Qiu, A. A. Litonjua, A. Damask, R. Lazarus, B. Klanderman, C. G. Irvin, S. P. Peters, J. P. Hanrahan, J. J. Lima, Fernando Martinez, D. Mauger, V. M. Chinchilli, M. Soto-Quiros, L. Avila, J. C. Celedón, C. Lange, S. T. WeissK. G. Tantisira

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Reversibility of airway obstruction in response to β 2 -agonists is highly variable among asthmatics, which is partially attributed to genetic factors. In a genome-wide association study of acute bronchodilator response (BDR) to inhaled albuterol, 534 290 single-nucleotide polymorphisms (SNPs) were tested in 403 white trios from the Childhood Asthma Management Program using five statistical models to determine the most robust genetic associations. The primary replication phase included 1397 polymorphisms in three asthma trials (pooled n=764). The second replication phase tested 13 SNPs in three additional asthma populations (n=241, n=215 and n=592). An intergenic SNP on chromosome 10, rs11252394, proximal to several excellent biological candidates, significantly replicated (P=1.98 × 10 -7) in the primary replication trials. An intronic SNP (rs6988229) in the collagen (COL22A1) locus also provided strong replication signals (P=8.51 × 10 -6). This study applied a robust approach for testing the genetic basis of BDR and identified novel loci associated with this drug response in asthmatics.

Original languageEnglish (US)
Pages (from-to)41-47
Number of pages7
JournalPharmacogenomics Journal
Volume14
Issue number1
DOIs
StatePublished - Feb 2014

Fingerprint

Genome-Wide Association Study
Bronchodilator Agents
Single Nucleotide Polymorphism
Asthma
Chromosomes, Human, Pair 10
Albuterol
Genetic Testing
Statistical Models
Airway Obstruction
Collagen
Pharmaceutical Preparations
Population

Keywords

  • albuterol
  • asthma; bronchodilator response
  • genome-wide association study
  • pharmacogenetics

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

Duan, Q. L., Lasky-Su, J., Himes, B. E., Qiu, W., Litonjua, A. A., Damask, A., ... Tantisira, K. G. (2014). A genome-wide association study of bronchodilator response in asthmatics. Pharmacogenomics Journal, 14(1), 41-47. https://doi.org/10.1038/tpj.2013.5

A genome-wide association study of bronchodilator response in asthmatics. / Duan, Q. L.; Lasky-Su, J.; Himes, B. E.; Qiu, W.; Litonjua, A. A.; Damask, A.; Lazarus, R.; Klanderman, B.; Irvin, C. G.; Peters, S. P.; Hanrahan, J. P.; Lima, J. J.; Martinez, Fernando; Mauger, D.; Chinchilli, V. M.; Soto-Quiros, M.; Avila, L.; Celedón, J. C.; Lange, C.; Weiss, S. T.; Tantisira, K. G.

In: Pharmacogenomics Journal, Vol. 14, No. 1, 02.2014, p. 41-47.

Research output: Contribution to journalArticle

Duan, QL, Lasky-Su, J, Himes, BE, Qiu, W, Litonjua, AA, Damask, A, Lazarus, R, Klanderman, B, Irvin, CG, Peters, SP, Hanrahan, JP, Lima, JJ, Martinez, F, Mauger, D, Chinchilli, VM, Soto-Quiros, M, Avila, L, Celedón, JC, Lange, C, Weiss, ST & Tantisira, KG 2014, 'A genome-wide association study of bronchodilator response in asthmatics', Pharmacogenomics Journal, vol. 14, no. 1, pp. 41-47. https://doi.org/10.1038/tpj.2013.5
Duan QL, Lasky-Su J, Himes BE, Qiu W, Litonjua AA, Damask A et al. A genome-wide association study of bronchodilator response in asthmatics. Pharmacogenomics Journal. 2014 Feb;14(1):41-47. https://doi.org/10.1038/tpj.2013.5
Duan, Q. L. ; Lasky-Su, J. ; Himes, B. E. ; Qiu, W. ; Litonjua, A. A. ; Damask, A. ; Lazarus, R. ; Klanderman, B. ; Irvin, C. G. ; Peters, S. P. ; Hanrahan, J. P. ; Lima, J. J. ; Martinez, Fernando ; Mauger, D. ; Chinchilli, V. M. ; Soto-Quiros, M. ; Avila, L. ; Celedón, J. C. ; Lange, C. ; Weiss, S. T. ; Tantisira, K. G. / A genome-wide association study of bronchodilator response in asthmatics. In: Pharmacogenomics Journal. 2014 ; Vol. 14, No. 1. pp. 41-47.
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