title: A genome-wide association study of bronchodilator response in asthmatics.
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.
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Q L
authors.initials: QL
authors.lastname: Duan
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lasky-Su
authors.affiliation: 1] Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Center for Genomic Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Himes
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Qiu
authors.affiliation: 1] Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Pulmonary Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Litonjua
authors.affiliation: Novartis, Cambridge, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Damask
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Lazarus
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Klanderman
authors.affiliation: Vermont Lung Center, Department of Medicine and Physiology, University of Vermont, Burlington, Vermont, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Irvin
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Peters
authors.affiliation: Pulmatrix, Lexington, MA, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Hanrahan
authors.affiliation: Nemours Children's Clinic, Centers for Clinical Pediatric Pharmacology and Pharmacogenetics, Jacksonville, FL, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lima
authors.affiliation: Arizona Respiratory Center and BIO5 Institute, University of Arizona, Tucson, AZ, USA.
authors.forename: F D
authors.initials: FD
authors.lastname: Martinez
authors.affiliation: Department of Public Health Sciences, Pennsylvania State University, Hershey, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Mauger
authors.affiliation: Department of Public Health Sciences, Pennsylvania State University, Hershey, PA, USA.
authors.forename: V M
authors.initials: VM
authors.lastname: Chinchilli
authors.affiliation: Hospital Nacional de Niños, San José, Costa Rica.
authors.forename: M
authors.initials: M
authors.lastname: Soto-Quiros
authors.affiliation: Hospital Nacional de Niños, San José, Costa Rica.
authors.forename: L
authors.initials: L
authors.lastname: Avila
authors.affiliation: Division of Pediatric Pulmonary Medicine, Allergy and Immunology, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Celedón
authors.affiliation: Harvard School of Public Health, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lange
authors.affiliation: 1] Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Center for Genomic Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [3] Pulmonary Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [4] Harvard School of Public Health, Boston, MA, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Weiss
authors.affiliation: 1] Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Pulmonary Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: K G
authors.initials: KG
authors.lastname: Tantisira
mesh_terms: D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents