A genome-wide analysis of the response to inhaled β2-agonists in chronic obstructive pulmonary disease

Short-acting β 2 -agonist bronchodilators are the most common medications used in treating chronic obstructive pulmonary disease (COPD). Genetic variants determining bronchodilator responsiveness (BDR) in COPD have not been identified. We performed a genome-wide association study (GWAS) of BDR in 5789 current or former smokers with COPD in one African-American and four white populations. BDR was defined as the quantitative spirometric response to inhaled β 2 -agonists. We combined results in a meta-analysis. In the meta-analysis, single-nucleotide polymorphisms (SNPs) in the genes KCNK1 ( P =2.02 × 10 −7 ) and KCNJ2 ( P =1.79 × 10 −7 ) were the top associations with BDR. Among African Americans, SNPs in CDH13 were significantly associated with BDR ( P =5.1 × 10 −9 ). A nominal association with CDH13 was identified in a gene-based analysis in all subjects. We identified suggestive association with BDR among COPD subjects for variants near two potassium channel genes ( KCNK1 and KCNJ2 ). SNPs in CDH13 were significantly associated with BDR in African Americans.