title: Genome-Wide Association Study Identifies Novel Pharmacogenomic Loci For Therapeutic Response to Montelukast in Asthma.
abstract: BACKGROUND
  Genome-wide association study (GWAS) is a powerful tool to identify novel pharmacogenetic single nucleotide polymorphisms (SNPs). Leukotriene receptor antagonists (LTRAs) are a major class of asthma medications, and genetic factors contribute to variable responses to these drugs. We used GWAS to identify novel SNPs associated with the response to the LTRA, montelukast, in asthmatics.
  
  
  METHODS
  Using genome-wide genotype and phenotypic data available from American Lung Association - Asthma Clinical Research Center (ALA-ACRC) cohorts, we evaluated 8-week change in FEV1 related to montelukast administration in a discovery population of 133 asthmatics. The top 200 SNPs from the discovery GWAS were then tested in 184 additional samples from two independent cohorts.
  
  
  RESULTS
  Twenty-eight SNP associations from the discovery GWAS were replicated. Of these, rs6475448 achieved genome-wide significance (combined P = 1.97 x 10-09), and subjects from all four studies who were homozygous for rs6475448 showed increased ΔFEV1 from baseline in response to montelukast.
  
  
  CONCLUSIONS
  Through GWAS, we identified a novel pharmacogenomic locus related to improved montelukast response in asthmatics.
authors.affiliation: Channing Division of Network Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
authors.forename: Amber
authors.initials: A
authors.lastname: Dahlin
authors.affiliation: Channing Division of Network Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, United States of America; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
authors.forename: Augusto
authors.initials: A
authors.lastname: Litonjua
authors.affiliation: Nemours Children's Clinic, Jacksonville, FL, United States of America.
authors.forename: John J
authors.initials: JJ
authors.lastname: Lima
authors.affiliation: Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
authors.affiliation: Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: University of Vermont, Burlington, VT, United States of America.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Irvin
authors.affiliation: Wake Forest School of Medicine, Winston-Salem, NC, United States of America.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Peters
authors.affiliation: Channing Division of Network Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, United States of America; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
authors.forename: Kelan G
authors.initials: KG
authors.lastname: Tantisira
mesh_terms: D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D003521:Cyclopropanes; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D013440:Sulfides; D016896:Treatment Outcome
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D011804:Quinolines; D013440:Sulfides; C093875:montelukast