Gene-based association identifies SPATA13-AS1 as a pharmacogenomic predictor of inhaled short-acting beta-agonist response in multiple population groups

Abstract

Inhaled short-acting beta-agonist (SABA) medication is commonly used in asthma patients to rapidly reverse airway obstruction and improve acute symptoms. We performed a genome wide association study of SABA medication response using gene-based association tests. A linear mixed model approach was first used for SNP associations, and results were later combined using GATES to generate gene-based associations. Our results identified SPATA13-AS1 as being significantly associated with SABA bronchodilator response in 328 healthy African Americans. In replication, this gene was associated with SABA response among 2 separate groups of African Americans with asthma (n=1,073, p=0.011 and n=1,968, p=0.014), 149 healthy African Americans (p=0.003), and 556 European Americans with asthma (p=0.041). SPATA13-AS1 was also associated with longitudinal SABA medication usage in 2 separate groups of African Americans with asthma (n=658, p=0.047 and n=1,968, p=0.025). Future studies are needed to delineate the precise mechanism by which SPATA13-AS1 may influence SABA response.

Genome-Wide Association Study of Short-Acting β2-Agonists. A Novel Genome-Wide Significant Locus on Chromosome 2 near ASB3

“…Although the SPATS2L variant was not genotyped on the platform used in this analysis, other SNPs in this region were associated with BDR in this analysis (e.g., rs4233996; P = 6.4 3 10 24 ). Using a gene-based GWAS approach, Padhukasahasram and colleagues (41) have identified a gene, SPATA13-AS1, associated with BDR in multiple cohorts, although no individual SNP demonstrated consistent effects. Another recent genomewide study identified associations with BDR in a large combined cohort of Latinos and Hispanics.…”

Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians

“…Furthermore, the type I error rate is well controlled and independent of gene size and linkage-disequilibrium pattern among markers 14 . The GATES method has been adopted by many genome-wide gene-based studies 15–18 . To explore whether the identified gene-based signal was driven by the most significant SNP in the gene, we performed sensitivity analysis excluding the most significant SNP in the identified gene using GATES method.…”

Omalizumab for severe allergic asthma in clinical trials and real-life studies: What we know and what we should address

“…Data about ethnicity, weight and BMI are not homogeneously and systematically reported so that a comparative analysis couldn't be effectively performed. It is not negligible as pharmaco-genetic features and consequently a responder/not responder profile may strictly depend on ethnicity [42], and the impact of the treatment on asthma could be different in obese patients. Reactivity to at least one perennial allergen is an inclusion criterion for RCTs; as far as R-L studies data about sensitization profile are often missing or not complete.…”