NHLBI TOPMed: Study of African Americans, Asthma, Genes and Environment (SAGE) Study
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ABSTRACT: This is a parallel case-control pharmacogenetic study of bronchodilator drug response among African American children with and without asthma. Each participant had spirometry measured using the KoKo PFT System. Asthmatic participants were administered with 4 puffs of HFA Albuterol. Healthy participants were given a baseline spirometry test. The overall goal is to identify genetic factors which are predictive of drug response in children with asthma. The principal tools include a questionnaire and biological specimen collection. Participants were 8-21 years old at time of recruitment. Children with asthma have physician-diagnosed asthma, symptoms and medications.
SECONDARY ACCESSION(S): PRJNA285276PRJNA285275
REPOSITORIES: dbGaP
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Project description:<p>This is a case-only pharmacogenetic study of bronchodilator drug response among racially admixed Latino children with asthma. Each participant had two spirometry measurements using the KoKo PFT System. With the first spirometry test, participant was administered with 4 puffs of HFA Albuterol. The second albuterol measurement was based on age, for participants under 16 years of age, additional 2 puffs were administered and for those over 16 years of age, additional 4 puffs were administered. The overall goal is to identify genetic factors which are predictive of drug response in children with asthma. The principal tools include a questionnaire and biological specimen collection. Participants are 8-21 years old at time of recruitment. Children with asthma have physician-diagnosed asthma, symptoms and medications.</p> <p>Comprehensive phenotypic data for GALAII study participants are available through dbGaP <a href="./study.cgi?study_id=phs001180">phs001180</a>.</p>
| phs000920 | dbGaP
Project description:<p>A case-control pharmacogenetic study of bronchodilator drug response among racially admixed Latino children with asthma. Each participant had two spirometry measurements using the KoKo PFT System. With the first spirometry test, participant was administered with 4 puffs of HFA Albuterol. The second albuterol measurement was based on age, for participants under 16 years of age, additional 2 puffs were administered and for those over 16 years of age, additional 4 puffs were administered. The overall goal is to identify genetic factors which are predictive of drug response in children with asthma. The principal tools include a questionnaire and biological specimen collection. Participants are 8-21 years old at time of recruitment. Children with asthma have physician-diagnosed asthma, symptoms and medications.</p> <p>The GALAII Study is utilized in the following dbGaP substudies. To view genotypes, analysis, other molecular data, and derived variables collected in these substudies, please click on the following substudies below or in the "Substudies" box located on the right hand side of this top-level study page phs001180 GALAII Study. <ul> <li><a href="./study.cgi?study_id=phs001274">phs001274</a>phs001274 GALAII GWAS</li> </ul> </p>
| phs001180 | dbGaP
Project description:<p>A Case pharmacogenetic study of bronchodilator drug response (Albuterol) among racially admixed Latino children with asthma between the ages of 8-40. Lung function testing was performed using the KoKo PFT system and each participant was administered albuterol dependent on age. Participants under 16 years of age, were administered 2 puffs of albuterol from a standard metered dose inhaler and 4 puffs for participants over 16 years old.</p> <p>The overall goal is to identify genetic factors which are predictive of drug response in children with asthma. The principal tools include a questionnaire and biological specimen collection. Participants with asthma have physician-diagnosed asthma, symptoms and medications.</p>
| phs001542 | dbGaP
Project description:Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced changes in DNAm in airway epithelial cells and assess the potential functional consequences and biological pathways implicated. We followed a discovery and validation study design to characterize albuterol-induced DNAm changes in paired airway epithelial cultures stimulated in vitro with albuterol. In the discovery phase, an epigenome-wide association study (EWAS) using paired nasal epithelial cultures from Puerto Rican children (n=97) identified 22 CpGs genome-wide associated with repeated-use albuterol treatment (p<9x10-8). Albuterol predominantly induced a hypomethylation effect on CpGs captured by the EPIC array across the genome (probability of hypomethylation: 76%, p-value=3.3x10-5). DNAm changes on the CpGs cg23032799 (CREB3L1), cg00483640 (MYLK4-LINC01600), and cg05673431 (KSR1) were validated in nasal epithelia from 10 independent donors (false discovery rate [FDR]<0.05). The effect on the CpG cg23032799 (CREB3L1) was cross-tissue validated in bronchial epithelial cells at nominal level (p=0.030). DNAm changes in these three CpGs showed to be influenced by three independent genetic variants (FDR<0.05). In silico analyses showed these polymorphisms regulated gene expression of nearby genes in lungs and/or fibroblasts including KSR1 and LINC01600 (6.30x10 14≤p≤6.60x10-5). Additionally, the hypomethylation at the CpGs cg10290200 (FLNC) and cg05673431 (KSR1) was associated with reduced gene expression of the genes where they are located (FDR<0.05). Furthermore, while the epigenetic effect of albuterol was independent of the asthma status, severity, and use of medication, BDR was nominally associated with the effect on the CpG cg23032799 (CREB3L1) (p=0.004). Gene-set enrichment analyses revealed that epigenomic modifications of albuterol could participate in asthma-relevant processes (e.g., IL-2, TNF-α, and NF-κB signaling pathways) and that albuterol-affected genes are likely regulated by Trichostatin A (FDR<0.05). Finally, nine differentially methylated regions were associated with albuterol treatment, including CREB3L1, MYLK4, and KSR1 (adjusted p-value<0.05). In conclusion, this study reveals, for the first time, evidence of epigenetic modifications induced by albuterol in the mucociliary airway epithelium. The epigenomic response induced by albuterol might have potential clinical implications by affecting biological pathways relevant to asthma
2023-10-18 | GSE240155 | GEO
Project description:BACKGROUND: Evaluation of the airway transcriptome may reveal patterns of gene expression that are associated with clinical phenotypes of asthma. To define transcriptomic endotypes of asthma (TEA) we analyzed gene expression in induced sputum that correlate with phenotypes of disease. METHODS: Gene expression was measured in sputum of subjects with asthma using Affymetrix HuGene ST 1.0 microarrays. Unsupervised clustering analysis of genes in pathways selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) identified TEA clusters. Clinical characteristics were compared and logistic regression analysis of matched blood samples defined an expression profile to determine the TEA cluster assignment in a cohort of children with asthma for validation. RESULTS: Three TEA clusters were identified. TEA cluster 1 had the most subjects with a history of intubation (P = 0.05), a lower pre-bronchodilator FEV1 (P = 0.006), a higher bronchodilator response (P = 0.03), and higher exhaled nitric oxide levels (P = 0.04), compared to the other TEA clusters. TEA cluster 2, the smallest cluster had the most subjects that were hospitalized for asthma (P = 0.04). Subjects in TEA cluster 3, the largest cluster, had normal lung function, low exhaled nitric oxide levels, and lower inhaled steroid requirements. Evaluation of TEA clusters in children confirmed that TEA clusters 1 and 2 are associated with a history of intubation (P = 5.58 x 10-06) and hospitalization (P = 0.01), respectively. CONCLUSIONS: Patterns of gene expression in the sputum and blood reveal TEA clusters that are associated with severe asthma phenotypes in children and adults. Gene expression was measured in sputum of subjects with asthma using Affymetrix HuGene ST 1.0 microarrays. Unsupervised clustering analysis of genes in pathways selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) identified TEA clusters. Clinical characteristics were compared and logistic regression analysis of matched blood samples defined an expression profile to determine the TEA cluster assignment in a cohort of children with asthma for validation.
2014-04-07 | E-GEOD-56396 | biostudies-arrayexpress
Project description:Rationale: Asthma is a chronic inflammatory airway disease. Children with severe asthma have lower levels of vitamin D than children with moderate asthma, and among children with severe asthma, airway smooth muscle (ASM) mass is inversely related to vitamin D levels. Beta2 agonists are a common asthma medication that act partly by targetting the ASM. We used RNA-Seq to characterize the human ASM transcriptome of fatal and asthma vs. contols at baseline and under two treatment conditions. Methods: The Illumina TruSeq assay was used to prepare 75bp paired-end libraries for ASM cells from white donors, 6 with fatal asthma and 12 control donors under three treatment conditions: 1) no treatment; 2) treatment with a β2-agonist (i.e. Albuterol, 1μM for 18h); 3) treatment with vitamin D 100 nM for 18h). Llibraries were sequenced with an Illumina Hi-Seq 2000 instrument. The Tuxedo Suite Tools were used to align reads to the hg19 reference genome, assemble transcripts, and perform differential expression analysis using the protocol described in https://github.com/blancahimes/taffeta
2014-12-01 | GSE58434 | GEO
Project description:Small RNA was sequenced from banked peripheral blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into high and low bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N= 277) vs low (N= 278) BDR group. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed. Results: We identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR=2.26) between high and low BDR group. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways.
2023-10-09 | GSE244573 | GEO
Project description:Rationale: Asthma is a chronic inflammatory airway disease. The most common medications used for its treatment are β2-agonists and glucocorticosteroids, and one of the primary tissues that these drugs target in the treatment of asthma is the airway smooth muscle. We used RNA-Seq to characterize the human airway smooth muscle (HASM) transcriptome at baseline and under three asthma treatment conditions. Methods: The Illumina TruSeq assay was used to prepare 75bp paired-end libraries for HASM cells from four white male donors under four treatment conditions: 1) no treatment; 2) treatment with a β2-agonist (i.e. Albuterol, 1μM for 18h); 3) treatment with a glucocorticosteroid (i.e. Dexamethasone (Dex), 1μM for 18h); 4) simultaneous treatment with a β2-agonist and glucocorticoid, and the libraries were sequenced with an Illumina Hi-Seq 2000 instrument. The Tuxedo Suite Tools were used to align reads to the hg19 reference genome, assemble transcripts, and perform differential expression analysis using the protocol described in https://github.com/blancahimes/taffeta mRNA profiles obtained via RNA-Seq for four primary human airway smooth muscle cell lines that were treated with dexamethasone, albuterol, dexamethasone+albuterol or were left untreated.
2014-01-01 | E-GEOD-52778 | biostudies-arrayexpress
Project description:Blood serum from 160 Childhood Asthma Management Program (CAMP) subjects were microRNA profiles with 13 subjects profiled twice. Each subject has diverse clinical phenotypes notably spirometry related phenotypes.
2016-06-09 | GSE74770 | GEO
Project description:A Genome-Wide Association Study for Post-bronchodilator Lung Function in Children with Asthma
| PRJNA343576 | ENA