Genome-wide association study of short-acting b2-agonists. A novel genome-wide significant locus on chromosome 2 near XXXX .

@entity71371 @entity565 @entity71372 @entity71375 @entity71373 @entity71374 @entity3834
RATIONALE: b2-Agonists are the most common form of treatment of @entity565 , but there is significant variability in response to these medications. A significant proportion of this responsiveness may be heritable. OBJECTIVES: To investigate whether a genome-wide association study (GWAS) could identify novel pharmacogenetic loci in @entity565 . METHODS: We performed a GWAS of acute bronchodilator response (BDR) to inhaled b2-agonists. A total of 444,088 single-nucleotide polymorphisms (SNPs) were examined in 724 individuals from the SNP Health Association Resource (SHARe) Asthma Resource Project ( @entity3834 ). The top 50 SNPs were carried forward to replication in a population of 444 individuals. MEASUREMENTS AND MAIN RESULTS: The combined P value for four SNPs reached statistical genome-wide significance aftercorrecting for multiple comparisons. Combined P values for @entity71371 , @entity71372 , @entity71373 , and @entity71374 were 2.21   *   10(-10), 5.75   *   10(-8), 9.3   *   10(-8), and 3.95   *   10(-8), respectively. The significant variants all map to a novel genetic region on chromosome 2 near the @entity71375 gene, a region associated with smooth muscle proliferation. As compared with the wild type, the presence of the minor alleles reduced the degree of BDR by 20% in the original population and by a similar percentage in the confirmatory population. CONCLUSIONS: These GWAS findings for BDR in subjects with @entity565 suggest that a gene associated with smooth muscle proliferation may influence a proportion of the smooth muscle relaxation that occurs in @entity565 .
