Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma
Mak ACY, White MJ, Eckalbar WL, Szpiech ZA, Oh SS, Pino-Yanes M, Hu D, Goddard P, Huntsman S, Galanter J, Wu AC, Himes BE, Germer S, Vogel JM, Bunting KL, Eng C, Salazar S, Keys KL, Liberto J, Nuckton TJ, Nguyen TA, Torgerson DG, Kwok PY, Levin AM, Celedón JC, Forno E, Hakonarson H, Sleiman PM, Dahlin A, Tantisira KG, Weiss ST, Serebrisky D, Brigino-Buenaventura E, Farber HJ, Meade K, Lenoir MA, Avila PC, Sen S, Thyne SM, Rodriguez-Cintron W, Winkler CA, Moreno-Estrada A, Sandoval K, Rodriguez-Santana JR, Kumar R, Williams LK, Ahituv N, Ziv E, Seibold MA, Darnell RB, Zaitlen N, Hernandez RD, Burchard EG; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium. Whole-Genome Sequencing of Pharmacogenetic Drug Response in Racially Diverse Children with Asthma. Am J Respir Crit Care Med. 2018 Jun 15;197(12):1552-1564.
American journal of respiratory and critical care medicine
RATIONALE: Albuterol, a bronchodilator medication, is the first-line therapy for asthma worldwide. There are significant racial/ethnic differences in albuterol drug response.
OBJECTIVES: To identify genetic variants important for bronchodilator drug response (BDR) in racially diverse children.
METHODS: We performed the first whole-genome sequencing pharmacogenetics study from 1,441 children with asthma from the tails of the BDR distribution to identify genetic association with BDR.
MEASUREMENTS AND MAIN RESULTS: We identified population-specific and shared genetic variants associated with BDR, including genome-wide significant (P < 3.53 × 10
CONCLUSIONS: The lack of minority data, despite a collaboration of eight universities and 13 individual laboratories, highlights the urgent need for a dedicated national effort to prioritize diversity in research. Our study expands the understanding of pharmacogenetic analyses in racially/ethnically diverse populations and advances the foundation for precision medicine in at-risk and understudied minority populations.
Medical Subject Headings
Adolescent; African Americans; Albuterol; Asthma; Bronchodilator Agents; Child; Female; Genome-Wide Association Study; Hispanic Americans; Humans; Male; Mexican Americans; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Race Factors; United States