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A GENOME-WIDE ASSOCIATION STUDY OF SEVERE ASTHMA EXACERBATIONS IN LATINO CHILDREN AND ADOLESCENTS
Yanes, Maria Pino et al. | Date Issued: 2020
Author
Yanes, Maria Pino
Qi, Cancan
Rios, Raimon
Han, Yueh-Ying
Kim, Soyeon
Oh, Sam
Pérez, Edna Acosta
Zhang, Rong
Hu, Donglei
Eng, Celeste
Huntsman, Scott
Avila, Lydiana
Boutaoui, Nadia
Cloutier, Michelle M.
Quiros, Manuel E. Soto
Xu, Cheng-jian
Weiss, Scott T.
Lasky-Su, Jessica
Kiedrowski, Megan R.
Figueiredo, Camila
Bomberger, Jennifer
Barreto, Mauricio Lima
Canino, Glorisa
Chen, Wei
Koppelman, Gerard H.
Burchard, Esteban G.
Celedón, Juan C.
Affilliation
"Múltipla ver em Notas"
Abstract
Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups. To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4,010 Latino youth with asthma in four independent cohorts, including 1,693 Puerto Ricans, 1,019 Costa Ricans, 640 Mexicans, 256 Brazilians, and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus (mQTL), expression quantitative trait locus (eQTL), and expression quantitative trait methylation (eQTM) analyses to assess whether the top SNP in the meta-analysis is linked to DNA methylation and gene expression in nasal (airway) epithelium in separate cohorts of Puerto Rican and Dutch children and adolescents. In the meta-analysis of GWAS, a SNP in FLJ22447 (rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbations (95% confidence interval= 1.34 to 1.79, P=6.3×10-9). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the FLJ22447 locus, which was in turn associated with increased expression of KCNJ2-AS1 in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, P=2.18 x 10-7). Thus, SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in FLJ22447 and severe asthma exacerbations in Latino youth. This may be partly explained by changes in airway epithelial expression of a gene recently implicated in atopic asthma in Puerto Rican children and adolescents (KCNJ2-AS1).
Keywords in Portuguese
Adolescente
Asma
Criança
Estudo de Associação Genômica Ampla
Custos de Cuidados de Saúde
 
Keywords
Adolescent
Asthma
Children
Genome-Wide Association Study
Health Care Costs
 
Publisher
European Respiratory Society
Citation
YANES, Maria Pino et al. A genome-wide association study of severe asthma exacerbations in Latino children and adolescents. European Respiratory Journal, 2020.
Notes
BARRETO, Maurício Lima. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. “Documento protegido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. 1Division of Pediatric Pulmonary Medicine, UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA. 2Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, La Laguna, Santa Cruz de Tenerife, Spain. 3CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. 4University of Groningen, University Medical Center Groningen, Dept. of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children’s Hospital, and 5University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands. 6Instituto de Ciências da Saúde, Universidade Federal da Bahia, Vale do Canela, Salvador, Bahia, Brazil. 7Department of Medicine, University of California San Francisco, San Francisco, CA, USA. 8Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico. 9Department of Pediatrics, Hospital Nacional de Niños, San José, Costa Rica. 10Department of Pediatrics, University of Connecticut, Farmington, CT, USA. 11CiiM and TWINCORE, joint ventures between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany. 12Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands. 13Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA. 14Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA. 15Instituto de Saúde Coletiva, Federal University of Bahia, Salvador, Brazil.