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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:148

Article

Akenroye, Ayobami T.¹  Brunetti, Tonya⁴  Romero, Karina^2,5  Daya, Michelle⁴  Kanchan, Kanika³  Shankar, Gautam³  Chavan, Sameer⁴  Boorgula, Meher Preethi⁴  Ampleford, Elizabeth A.⁶  Fonseca, Hellen Freitas⁷  Hawkins, Gregory A.⁸  Teixeira, Helena Mariana Pitangueira⁷  Campbell, Monica⁴  Rafaels, Nicholas⁴  Winters, Alexandra³  Bleecker, Eugene R.⁹  Cruz, Alvaro A.¹⁰  Barreto, Mauricio L.¹¹  Meyers, Deborah A.⁹  Ortega, Victor E.⁶  Figueiredo, Camila A.⁷  Barnes, Kathleen C.⁴  Checkley, William^2,12  Hansel, Nadia N.²  Mathias, Rasika A.³ 

[1] Johns Hopkins Univ, Sch Med, Div Pediat Allergy & Immunol, Baltimore, MD 21224 USA

[2] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA

[3] Johns Hopkins Univ, Sch Med, Div Allergy & Clin Immunol, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA

[4] Univ Colorado, Div Biomed Informat & Personalized Med, Denver, CO 80202 USA

[5] AB PRISMA, Lima, Peru

[6] Wake Forest Sch Med, Ctr Precis Med, Dept Internal Med, Winston Salem, NC 27101 USA

[7] Univ Fed Bahia UFBA, Inst Ciencias Saude, Salvador, BA, Brazil

[8] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC 27101 USA

[9] Univ Arizona, Dept Med, Tucson, AZ USA

[10] Fundacao ProAR, Salvador, BA, Brazil

[11] Fiocruz MS, Ctr Integracao Dados & Conhecimento Saude, Salvador, BA, Brazil

[12] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Program Global Dis Epidemiol & Control, Baltimore, MD USA

关键词: Asthma;    immunoglobulin E;    lung function;    admixture;    genome wide association analyses;    Peru;    ancestry;    allergy;    Abbreviations used;    Populations;   

DOI  :  10.1016/j.jaci.2021.02.035

来源: Elsevier

【 摘 要 】

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 x 10-10) and was independent of an association with the haplotype HLA-DQA1-HLA-DQB1:04.01-04.02 (P = 1.55 x 10-05). For lung function, we identified a locus (rs4410198; P = 5.536 x 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. (J Allergy Clin Immunol 2021;148:1493-504.)

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