Ayobami T Akenroye1, Tonya Brunetti2, Karina Romero3, Michelle Daya2, Kanika Kanchan4, Gautam Shankar4, Sameer Chavan2, Meher Preethi Boorgula2, Elizabeth A Ampleford5, Héllen Freitas Fonseca6, Gregory A Hawkins7, Helena Mariana Pitangueira Teixeira6, Monica Campbell2, Nicholas Rafaels2, Alexandra Winters4, Eugene R Bleecker8, Alvaro A Cruz9, Mauricio L Barreto10, Deborah A Meyers8, Victor E Ortega5, Camila A Figueiredo6, Kathleen C Barnes2, William Checkley11, Nadia N Hansel12, Rasika A Mathias13. 1. Division of Pediatric Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md. 2. Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Denver, Colo. 3. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Md; A.B. PRISMA, Lima, Peru. 4. Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md. 5. Department of Internal Medicine, Center for Precision Medicine, Wake Forest School of Medicine, Winston-Salem, NC. 6. Instituto de Ciências da Saúde, Universidade Federal da Bahia (UFBA), Salvador, Brazil. 7. Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC. 8. Department of Medicine, University of Arizona, Tucson, Ariz. 9. Fundação ProAR, Salvador, Brazil. 10. Centro de Integração de Dados e Conhecimento para Saúde, Fiocruz, Salvador, Brazil. 11. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Md; Department of International Health, Program in Global Disease Epidemiology and Control, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md. 12. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address: nhansel1@jhmi.edu. 13. Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address: rmathias@jhmi.edu.
Abstract
BACKGROUND: Genetic ancestry plays a role in asthma health disparities. OBJECTIVE: Our aim was to evaluate the impact of ancestry on and identify genetic variants associated with asthma, total serum IgE level, and lung function. METHODS: A total of 436 Peruvian children (aged 9-19 years) with asthma and 291 without asthma were genotyped by using the Illumina Multi-Ethnic Global Array. Genome-wide proportions of indigenous ancestry populations from continental America (NAT) and European ancestry from the Iberian populations in Spain (IBS) were estimated by using ADMIXTURE. We assessed the relationship between ancestry and the phenotypes and performed a genome-wide association study. RESULTS: The mean ancestry proportions were 84.7% NAT (case patients, 84.2%; controls, 85.4%) and 15.3% IBS (15.8%; 14.6%). With adjustment for asthma, NAT was associated with higher total serum IgE levels (P < .001) and IBS was associated with lower total serum IgE levels (P < .001). NAT was associated with higher FEV1 percent predicted values (P < .001), whereas IBS was associated with lower FEV1 values in the controls but not in the case patients. The HLA-DR/DQ region on chromosome 6 (Chr6) was strongly associated with total serum IgE (rs3135348; P = 3.438 × 10-10) and was independent of an association with the haplotype HLA-DQA1∼HLA-DQB1:04.01∼04.02 (P = 1.55 × 10-05). For lung function, we identified a locus (rs4410198; P = 5.536 × 10-11) mapping to Chr19, near a cluster of zinc finger interacting genes that colocalizes to the long noncoding RNA CTD-2537I9.5. This novel locus was replicated in an independent sample of pediatric case patients with asthma with similar admixture from Brazil (P = .005). CONCLUSION: This study confirms the role of HLA in atopy, and identifies a novel locus mapping to a long noncoding RNA for lung function that may be specific to children with NAT.
BACKGROUND: Genetic ancestry plays a role in asthma health disparities. OBJECTIVE: Our aim was to evaluate the impact of ancestry on and identify genetic variants associated with asthma, total serum IgE level, and lung function. METHODS: A total of 436 Peruvian children (aged 9-19 years) with asthma and 291 without asthma were genotyped by using the Illumina Multi-Ethnic Global Array. Genome-wide proportions of indigenous ancestry populations from continental America (NAT) and European ancestry from the Iberian populations in Spain (IBS) were estimated by using ADMIXTURE. We assessed the relationship between ancestry and the phenotypes and performed a genome-wide association study. RESULTS: The mean ancestry proportions were 84.7% NAT (case patients, 84.2%; controls, 85.4%) and 15.3% IBS (15.8%; 14.6%). With adjustment for asthma, NAT was associated with higher total serum IgE levels (P < .001) and IBS was associated with lower total serum IgE levels (P < .001). NAT was associated with higher FEV1 percent predicted values (P < .001), whereas IBS was associated with lower FEV1 values in the controls but not in the case patients. The HLA-DR/DQ region on chromosome 6 (Chr6) was strongly associated with total serum IgE (rs3135348; P = 3.438 × 10-10) and was independent of an association with the haplotype HLA-DQA1∼HLA-DQB1:04.01∼04.02 (P = 1.55 × 10-05). For lung function, we identified a locus (rs4410198; P = 5.536 × 10-11) mapping to Chr19, near a cluster of zinc finger interacting genes that colocalizes to the long noncoding RNA CTD-2537I9.5. This novel locus was replicated in an independent sample of pediatric case patients with asthma with similar admixture from Brazil (P = .005). CONCLUSION: This study confirms the role of HLA in atopy, and identifies a novel locus mapping to a long noncoding RNA for lung function that may be specific to children with NAT.
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