ArticleThe pharmacogenomics journal2015
Pharmacodynamic genome-wide association study identifies new responsive loci for glucocorticoid intervention in asthma.
Article in The pharmacogenomics journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
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Who cites it
13 citing papers in PubMed.
- Genome-wide association study of inhaled corticosteroid response in admixed children with asthma.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2019Trial
- Genetic Determinants of the Acute Respiratory Distress Syndrome.Journal of clinical medicine · 2023Review
- Multiomics analysis identifies BIRC3 as a novel glucocorticoid response-associated gene.The Journal of allergy and clinical immunology · 2022Article
- Identification ofJournal of personalized medicine · 2021Article
- Advances in Genomic Discovery and Implications for Personalized Prevention and Medicine: Estonia as Example.Journal of personalized medicine · 2021Review
- Insights into glucocorticoid responses derived from omics studies.Pharmacology & therapeutics · 2021Review
- Advances in asthma and allergic disease genetics: Is bigger always better?The Journal of allergy and clinical immunology · 2019Review
- Integrative approach identifies corticosteroid response variant in diverse populations with asthma.The Journal of allergy and clinical immunology · 2019Article
- A unified mapping framework of multifaceted pharmacodynamic responses to hypertension interventions.Drug discovery today · 2019Review
- Genetic associations of the response to inhaled corticosteroids in asthma: a systematic review.Clinical and translational allergy · 2019Review
- How does race and ethnicity effect the precision treatment of asthma?Expert review of precision medicine and drug development · 2019Article
- Mapping genes for drug chronotherapy.Drug discovery today · 2018Review
- Asthma Pharmacogenomics: 2015 Update.Current allergy and asthma reports · 2015Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Asthma is a chronic lung disease that has a high prevalence. The therapeutic intervention of this disease can be made more effective if genetic variability in patients' response to medications is implemented. However, a clear picture of the genetic architecture of asthma intervention response remains elusive. We conducted a genome-wide association study (GWAS) to identify drug response-associated genes for asthma, in which 909 622 SNPs were genotyped for 120 randomized participants who inhaled multiple doses of glucocorticoids. By integrating pharmacodynamic properties of drug reactions, we implemented a mechanistic model to analyze the GWAS data, enhancing the scope of inference about the genetic architecture of asthma intervention. Our pharmacodynamic model observed associations of genome-wide significance between dose-dependent response to inhaled glucocorticoids (measured as %FEV1) and five loci (P=5.315 × 10(-7) to 3.924 × 10(-9)), many of which map to metabolic genes related to lung function and asthma risk. All significant SNPs detected indicate a recessive effect, at which the homozygotes for the mutant alleles drive variability in %FEV1. Significant associations were well replicated in three additional independent GWAS studies. Pooled together over these three trials, two SNPs, chr6 rs6924808 and chr11 rs1353649, display an increased significance level (P=6.661 × 10(-16) and 5.670 × 10(-11)). Our study reveals a general picture of pharmacogenomic control for asthma intervention. The results obtained help to tailor an optimal dose for individual patients to treat asthma based on their genetic makeup.
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