%0 Journal Article %A Angel C. Y. Mak %A Marquitta J. White %A Zachary A. Szpiech %A Walter L. Eckalbar %A Sam S. Oh %A Maria Pino-Yanes %A Donglei Hu %A Scott Huntsman %A Joshua Galanter %A Dara G. Torgerson %A Ann Chen Wu %A Blanca E. Himes %A Soren Germer %A Julia M. Vogel %A Karen L. Bunting %A Celeste Eng %A Sandra Salazar %A Kevin L. Keys %A Thomas A. Nguyen %A Pui-Yan Kwok %A Albert M. Levin %A Juan C. Celedón %A Erick Forno %A Hakon Hakonarson %A Patrick M. Sleiman %A Amber Dahlin %A Kelan G. Tantisira %A Scott T. Weiss %A Denise Serebrisky %A Emerita Brigino-Buenaventura %A Harold J. Farber %A Kelley Meade %A Michael A. Lenoir %A Pedro C. Avila %A Saunak Sen %A Shannon M. Thyne %A William Rodriguez-Cintron %A Cheryl A. Winkler %A Andrés Moreno-Estrada %A Karla Sandoval %A Jose R. Rodriguez-Santana %A Rajesh Kumar %A L. Keoki Williams %A Nadav Ahituv %A Elad Ziv %A Max A. Seibold %A Robert B. Darnell %A Noah Zaitlen %A Ryan D. Hernandez %A Esteban G. Burchard %A the Trans-Omics for Precision Medicine Whole Genome Sequencing Program (TOPMed) Team These authors contributed equally to this work %T Whole Genome Sequencing of Pharmacogenetic Drug Response in Racially and Ethnically Diverse Children with Asthma %D 2017 %R 10.1101/128116 %J bioRxiv %P 128116 %X Albuterol, a bronchodilator medication, is the first-line therapy for asthma treatment worldwide. However it has a wide variation of drug response among different racial/ethnic groups. We performed the largest pharmacogenetics study to date, using whole genome sequencing data from 1,441 minority children with asthma from the extremes of bronchodilator drug response (BDR) to albuterol. We identified population-specific and shared pharmacogenetic variants associated with BDR, including genome-wide significant and suggestive loci near genes previously associated with lung capacity (DNAH5), immunity (NFKB1 and PLCB1), and β-adrenergic signaling pathways (ADAMTS3 and COX18). Functional assays revealed that the BDR-associated SNP within NFKB1 is in linkage disequilibrium with SNPs in a functionally active enhancer and is also associated with the expression of a neighboring gene SLC39A8. Our study expands the understanding of pharmacogenetic analyses in racially and ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations. %U https://www.biorxiv.org/content/biorxiv/early/2017/04/24/128116.full.pdf