RT Journal Article SR Electronic T1 Whole Genome Sequencing of Pharmacogenetic Drug Response in Racially and Ethnically Diverse Children with Asthma JF bioRxiv FD Cold Spring Harbor Laboratory SP 128116 DO 10.1101/128116 A1 Angel C. Y. Mak A1 Marquitta J. White A1 Zachary A. Szpiech A1 Walter L. Eckalbar A1 Sam S. Oh A1 Maria Pino-Yanes A1 Donglei Hu A1 Scott Huntsman A1 Joshua Galanter A1 Dara G. Torgerson A1 Ann Chen Wu A1 Blanca E. Himes A1 Soren Germer A1 Julia M. Vogel A1 Karen L. Bunting A1 Celeste Eng A1 Sandra Salazar A1 Kevin L. Keys A1 Thomas A. Nguyen A1 Pui-Yan Kwok A1 Albert M. Levin A1 Juan C. Celedón A1 Erick Forno A1 Hakon Hakonarson A1 Patrick M. Sleiman A1 Amber Dahlin A1 Kelan G. Tantisira A1 Scott T. Weiss A1 Denise Serebrisky A1 Emerita Brigino-Buenaventura A1 Harold J. Farber A1 Kelley Meade A1 Michael A. Lenoir A1 Pedro C. Avila A1 Saunak Sen A1 Shannon M. Thyne A1 William Rodriguez-Cintron A1 Cheryl A. Winkler A1 Andrés Moreno-Estrada A1 Karla Sandoval A1 Jose R. Rodriguez-Santana A1 Rajesh Kumar A1 L. Keoki Williams A1 Nadav Ahituv A1 Elad Ziv A1 Max A. Seibold A1 Robert B. Darnell A1 Noah Zaitlen A1 Ryan D. Hernandez A1 Esteban G. Burchard A1 the Trans-Omics for Precision Medicine Whole Genome Sequencing Program (TOPMed) Team These authors contributed equally to this work YR 2017 UL http://biorxiv.org/content/early/2017/04/24/128116.abstract AB 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.