- NIHPA Author Manuscripts
- PMC3706515
Pharmacogenomics J. Author manuscript; available in PMC Aug 1, 2014.
Published in final edited form as:
PMCID: PMC3706515
NIHMSID: NIHMS442409
A genome-wide association study of bronchodilator response in asthmatics
Qing Ling Duan, PhD,1,* Jessica Lasky-Su, ScD,1,* Blanca E. Himes, PhD,1,2 Weiliang Qiu, PhD,1 Augusto A. Litonjua, MD, MPH,1,3 Amy Damask, PhD,5 Ross Lazarus, MB, BS,1 Barbara Klanderman, PhD,1 Charles G. Irvin, PhD,6Stephen P. Peters, MD, PhD,7 John P. Hanrahan, MD, MPH,8 John J. Lima, PharmD,9 Fernando D. Martinez, MD,10David Mauger, PhD,11 Vernon M. Chinchilli, PhD,11 Manuel Soto-Quiros, PhD,12 Lydiana Avila, MD,12 Juan C. Celedón, MD, DrPH,13 Christoph Lange, PhD,4 Scott T. Weiss, MD, MS,1,2,3,4 and Kelan G. Tantisira, MD, MPH1,3
Abstract
Reversibility of airway obstruction in response to β2-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.
Keywords: pharmacogenetics, asthma, bronchodilator response, genome-wide association study, albuterol
Formats:
Abstract
Reversibility of airway obstruction in response to β2-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.
Keywords:
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