TY - JOUR
T1 - Genome-wide association study of asthma, total IgE, and lung function in a cohort of Peruvian children
AU - Akenroye, Ayobami T.
AU - Brunetti, Tonya
AU - Romero, Karina
AU - Daya, Michelle
AU - Kanchan, Kanika
AU - Shankar, Gautam
AU - Chavan, Sameer
AU - Preethi Boorgula, Meher
AU - Ampleford, Elizabeth A.
AU - Fonseca, Héllen Freitas
AU - Hawkins, Gregory A.
AU - Pitangueira Teixeira, Helena Mariana
AU - Campbell, Monica
AU - Rafaels, Nicholas
AU - Winters, Alexandra
AU - Bleecker, Eugene R.
AU - Cruz, Alvaro A.
AU - Barreto, Mauricio L.
AU - Meyers, Deborah A.
AU - Ortega, Victor E.
AU - Figueiredo, Camila A.
AU - Barnes, Kathleen C.
AU - Checkley, William
AU - Hansel, Nadia N.
AU - Mathias, Rasika A.
N1 - Funding Information:
Supported by National Institute of Environmental Health Sciences, National Institutes of Health (grants R01ES018845 and R01ES018845-S1 and NHLBI R01 HL142992 ). A.T.A was supported by the National Institute of Allergy and Infectious Diseases T32 Research Training Grant in Pediatric Allergy and Immunology (grant no. 2T32AI007007-41 ) and the Johns Hopkins University Provost’s Postdoctoral Award . K.R. was a Fogarty Global Health Fellow through the consortium comprising the University of North Carolina, Johns Hopkins University, Morehouse School of Medicine, and Tulane University during the conduct of this work (through grant 5R25TW009340) W.C. was supported by Pathway to Independence Award R00HL096955 from the National Heart, Lung, and Blood Institute, National Institutes of Health .
Publisher Copyright:
© 2021 American Academy of Allergy, Asthma & Immunology
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Asthma
KW - Peru
KW - admixture
KW - allergy
KW - ancestry
KW - genome wide association analyses
KW - immunoglobulin E
KW - lung function
UR - http://www.scopus.com/inward/record.url?scp=85104158983&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85104158983&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2021.02.035
DO - 10.1016/j.jaci.2021.02.035
M3 - Article
C2 - 33713768
AN - SCOPUS:85104158983
SN - 0091-6749
VL - 148
SP - 1493
EP - 1504
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -