TY - JOUR T1 - Whole Genome Sequencing of Pharmacogenetic Drug Response in Racially and Ethnically Diverse Children with Asthma JF - bioRxiv DO - 10.1101/128116 SP - 128116 AU - Angel C. Y. Mak AU - Marquitta J. White AU - Zachary A. Szpiech AU - Walter L. Eckalbar AU - Sam S. Oh AU - Maria Pino-Yanes AU - Donglei Hu AU - Scott Huntsman AU - Joshua Galanter AU - Dara G. Torgerson AU - Ann Chen Wu AU - Blanca E. Himes AU - Soren Germer AU - Julia M. Vogel AU - Karen L. Bunting AU - Celeste Eng AU - Sandra Salazar AU - Kevin L. Keys AU - Thomas A. Nguyen AU - Pui-Yan Kwok AU - Albert M. Levin AU - Juan C. Celedón AU - Erick Forno AU - Hakon Hakonarson AU - Patrick M. Sleiman AU - Amber Dahlin AU - Kelan G. Tantisira AU - Scott T. Weiss AU - Denise Serebrisky AU - Emerita Brigino-Buenaventura AU - Harold J. Farber AU - Kelley Meade AU - Michael A. Lenoir AU - Pedro C. Avila AU - Saunak Sen AU - Shannon M. Thyne AU - William Rodriguez-Cintron AU - Cheryl A. Winkler AU - Andrés Moreno-Estrada AU - Karla Sandoval AU - Jose R. Rodriguez-Santana AU - Rajesh Kumar AU - L. Keoki Williams AU - Nadav Ahituv AU - Elad Ziv AU - Max A. Seibold AU - Robert B. Darnell AU - Noah Zaitlen AU - Ryan D. Hernandez AU - Esteban G. Burchard AU - the Trans-Omics for Precision Medicine Whole Genome Sequencing Program (TOPMed) Team These authors contributed equally to this work Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/24/128116.abstract N2 - 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. ER -