A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma.

Autor: Spear ML; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA., Hu D; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Pino-Yanes M; Research Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Tenerife, Spain.; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.; Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, La Laguna, Tenerife, Spain., Huntsman S; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Eng C; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Levin AM; Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA., Ortega VE; Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston Salem, NC, USA., White MJ; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., McGarry ME; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, USA., Thakur N; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Galanter J; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA., Mak ACY; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Oh SS; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Ampleford E; Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston Salem, NC, USA., Peters SP; Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston Salem, NC, USA., Davis A; UCSF Benioff Children's Hospital Oakland, Center for Community Health and Engagement, Oakland, CA, USA., Kumar R; Ann & Robert H. Lurie Children's Hospital of Chicago, Pediatrics, Chicago, IL, USA., Farber HJ; Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA., Meade K; UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA., Avila PC; Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Serebrisky D; Pediatric Pulmonary Division, Jacobi Medical Center, Bronx, NY, USA.; Albert Einstein College of Medicine, Pediatrics, Bronx, NY, USA., Lenoir MA; Bay Area Pediatrics, Oakland, CA, USA., Brigino-Buenaventura E; Department of Allergy & Immunology, Kaiser Permanente-Vallejo Medical Center, Vallejo, CA, USA., Cintron WR; Veterans Caribbean Health System, San Juan, Puerto Rico., Thyne SM; Department of Pediatrics, David Geffen School of Medicine at ULCA, Olive View-UCLA Medical Center, Sylmar, CA, USA., Rodriguez-Santana JR; Centro de Neumologia Pediatrica, San Juan, Puerto Rico., Ford JG; Columbia University, New York, NY, USA., Chapela R; Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico., Estrada AM; National Laboratory of Genomics for Biodiversity (LANGEBIO), CINVESTAV, Irapuato, Guanajuato, Mexico., Sandoval K; National Laboratory of Genomics for Biodiversity (LANGEBIO), CINVESTAV, Irapuato, Guanajuato, Mexico., Seibold MA; Department of Pediatrics, National Jewish Health, Denver, CO, USA., Winkler CA; Basic Research Laboratory, National Cancer Institute, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD, USA., Bleecker ER; Department of Medicine, The University of Arizona, Tucson, AZ, USA., Myers DA; Department of Medicine, The University of Arizona, Tucson, AZ, USA., Williams LK; Center for Health Policy and Health Services Research,, Henry Ford Health System, Detroit, MI, USA.; Department of Internal Medicine, Henry Ford Health System, Detroit, MI, USA., Hernandez RD; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.; California Institute for Quantitative Biosciences (QB3), University of California, San Francisco, CA, USA.; Institute for Human Genetics, University of California, San Francisco, CA, USA., Torgerson DG; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA., Burchard EG; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA. esteban.burchard@ucsf.edu.; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. esteban.burchard@ucsf.edu.
Jazyk: angličtina
Zdroj: The pharmacogenomics journal [Pharmacogenomics J] 2019 Jun; Vol. 19 (3), pp. 249-259. Date of Electronic Publication: 2018 Sep 12.
DOI: 10.1038/s41397-018-0042-4
Abstrakt: Short-acting β 2 -adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10 -9 ). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10 -8 ). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.
Databáze: MEDLINE