A genome-wide association study of severe asthma exacerbations in Latino children and adolescents.

Qi Yan, Erick Forno, Esther Herrera-Luis, Maria Pino-Yanes, Cancan Qi, Raimon Rios, Yueh-Ying Han, Soyeon Kim, Sam Oh, Edna Acosta-Pérez, Rong Zhang, Donglei Hu, Celeste Eng, Scott Huntsman, Lydiana Avila, Nadia Boutaoui, Michelle M Cloutier, Manuel E Soto-Quiros, Cheng-Jian Xu, Scott T Weiss, Jessica Lasky-Su, Megan R Kiedrowski, Camila Figueiredo, Jennifer Bomberger, Mauricio L Barreto, Glorisa Canino, Wei Chen, Gerard H Koppelman, Esteban G Burchard, Juan C Celedón

Journal: The European respiratory journal 2021;57(4):2002693

PMID: 33093117

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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 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus, expression quantitative trait locus and expression quantitative trait methylation analyses to assess whether the top single nucleotide polymorphism (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, an SNP in (rs2253681) was significantly associated with 1.55 increased odds of severe asthma exacerbation (95% CI 1.34-1.79, p=6.3×10). This SNP was significantly associated with DNA methylation of a CpG site (cg25024579) at the locus, which was in turn associated with increased expression of in nasal airway epithelium from Puerto Rican children and adolescents (β=0.10, p=2.18×10).SNP rs2253681 was significantly associated with both DNA methylation of a cis-CpG in 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 ().

Address: Division of Pediatric Pulmonary Medicine, University of Pittsburgh Medical Centre, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.; Shared first authors.; Genomics and Health Group, Dept of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, La Laguna, Spain.; Shared first authors.; Genomics and Health Group, Dept of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna, La Laguna, Spain.; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.; Dept of Pediatric Pulmonology and Pediatric Allergy, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.; Division of Pediatric Pulmonary Medicine, University of Pittsburgh Medical Centre, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA.; Dept of Medicine, University of California San Francisco, San Francisco, CA, USA.; Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico.; Dept of Pediatrics, Hospital Nacional de Niños, San José, Costa Rica.; Dept of Pediatrics, University of Connecticut, Farmington, CT, USA.; CiiM and TWINCORE, joint ventures between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.; Dept of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Dept of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA.; Instituto de Saúde Coletiva, Federal University of Bahia, Salvador, Brazil.; Dept of Medicine, University of California San Francisco, San Francisco, CA, USA.; Shared senior authors.; Division of Pediatric Pulmonary Medicine, University of Pittsburgh Medical Centre, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA, USA [email protected].; Shared senior authors.

DOI: 10.1183/13993003.02693-2020

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MeSH Terms: Adolescent, Asthma, Brazil, Child, Genome-Wide Association Study, Hispanic or Latino, Humans, Puerto Rico