@article{4343926f4664409fb7833a531cf80a43,
title = "A genome-wide analysis of the response to inhaled β 2-agonists in chronic obstructive pulmonary disease",
abstract = "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.",
author = "M. Hardin and Cho, {M. H.} and McDonald, {M. L.} and E. Wan and Lomas, {D. A.} and Coxson, {H. O.} and W. MacNee and J. Vestbo and Yates, {J. C.} and A. Agusti and Calverley, {P. M.A.} and B. Celli and C. Crim and S. Rennard and E. Wouters and P. Bakke and Bhatt, {S. P.} and V. Kim and J. Ramsdell and Regan, {E. A.} and Make, {B. J.} and Hokanson, {J. E.} and Crapo, {J. D.} and Beaty, {T. H.} and Hersh, {C. P.}",
note = "Funding Information: We thank participants and field investigators in ECLIPSE, NETT, GenKOLS and COPDGene for their willingness to contribute to medical research. This study was supported by the US National Institutes of Health Grants R01 HL089897, R01 HL089856, K12 HL089990, R01 HL094635, P01 HL105339 and P01 HL083069 (National Heart, Lung, and Blood Institute) and R01 NR013377 (National Institute of Nursing Research); The Sheila J Goodnight, MD, FCCP Clinical Research Grant in Women's Lung Health; COPDGene project is also supported by the COPD Foundation through contributions made to an Industry Advisory Board comprising AstraZeneca, Pfizer, Siemens, Novartis, Boehringer Ingelheim, Sunovion and GlaxoSmithKline. ECLIPSE is supported by GlaxoSmithKline. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute, the National Institute of Nursing Research or the National Institutes of Health. Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited.",
year = "2016",
month = aug,
day = "1",
doi = "10.1038/tpj.2015.65",
language = "English (US)",
volume = "16",
pages = "326--335",
journal = "Pharmacogenomics Journal",
issn = "1470-269X",
publisher = "Nature Publishing Group",
number = "4",
}