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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 single-nucleotide polymorphism associations, and the 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 the two separate groups of African Americans with asthma (n=1073, P=0.011 and n=1968, 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 the two separate groups of African Americans with asthma (n=658, P=0.047 and n=1968, P=0.025). Future studies are needed to delineate the precise mechanism by which SPATA13-AS1 may influence SABA response.

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Acknowledgements

This work was supported by grants from the American Asthma Foundation (to EGB and LKW), the Flight Attendant Medical Research Institute (to EGB), the Fund for Henry Ford Hospital (to DEL and LKW), the Robert Wood Johnson Foundation Amos Medical Faculty Development Program (to EGB), the Sandler Foundation (to EGB) and the following institutes of the National Institutes of Health: National Institute of Allergy and Infectious Diseases (AI077439 to EGB; AI079139 and AI061774 to LKW), the National Heart Lung and Blood Institute (K23HL093023 to RK; HL078885, HL088133 and 5RC2HL101651 to EGB; and HL079055 and 5RC2HL101651 to LKW), the National Institute of Environmental Health Sciences (ES015794 to EGB), and the National Institute of Diabetes and Digestive and Kidney diseases (DK064695 to LKW).

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Correspondence to B Padhukasahasram.

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Padhukasahasram, B., Yang, J., Levin, A. et al. Gene-based association identifies SPATA13-AS1 as a pharmacogenomic predictor of inhaled short-acting beta-agonist response in multiple population groups. Pharmacogenomics J 14, 365–371 (2014). https://doi.org/10.1038/tpj.2013.49

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