Genome-wide association study of asthma, total IgE, and lung function in a cohort of Peruvian children

Ayobami T Akenroye; Tonya Brunetti; Karina Romero; Michelle Daya; Kanika Kanchan; Gautam Shankar; Sameer Chavan; Meher Preethi Boorgula; Elizabeth A Ampleford; Héllen Freitas Fonseca; Gregory A Hawkins; Helena Mariana Pitangueira Teixeira; Monica Campbell; Nicholas Rafaels; Alexandra Winters; Eugene R Bleecker; Alvaro A Cruz; Mauricio L Barreto; Deborah A Meyers; Victor E Ortega; Camila A Figueiredo; Kathleen C Barnes; William Checkley; Nadia N Hansel; Rasika A Mathias

doi:10.1016/j.jaci.2021.02.035

Genome-wide association study of asthma, total IgE, and lung function in a cohort of Peruvian children

J Allergy Clin Immunol. 2021 Dec;148(6):1493-1504. doi: 10.1016/j.jaci.2021.02.035. Epub 2021 Mar 10.

Authors

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

Affiliations

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.

Keywords: Asthma; Peru; admixture; allergy; ancestry; genome wide association analyses; immunoglobulin E; lung function.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Americas
Asthma / epidemiology
Asthma / genetics*
Child
Cohort Studies
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype*
HLA-DQ Antigens / metabolism
Humans
Immunoglobulin E / metabolism*
Indigenous Peoples*
Lung / immunology
Lung / metabolism*
Male
Peru / epidemiology
Polymorphism, Single Nucleotide
RNA, Long Noncoding / genetics
Spain
Young Adult

Substances

HLA-DQ Antigens
RNA, Long Noncoding
Immunoglobulin E

Abstract

Publication types

MeSH terms

Substances

Grants and funding