Multi-ethnic genome-wide and HLA association study of total serum IgE
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Author
Daya, MichelleCox, Corey
Acevedo, Nathalie
Boorgula, Meher P
Campbell, Monica
Chavan, Sameer
Cho, Michael H
David, Gloria L
Kachroo, Priyadarshini
Lasky-Su, Jessica
Li, Xingnan
McHugh, Caitlin P
Qiao, Dandi
Rafaels, Nicholas
Beck, Lisa A
Bleecker, Eugene R
Caraballo, Luis
Cupples, Adrienne L
Figueiredo, Camila A
Gallo, Richard L
Hanifin, Jon
Hansel, Nadia N
Hata, Tissa R
Hersh, Craig P
Knight-Madden, Jennifer
Leung, Donald Y M
Guttman-Yassky, Emma
Meyers, Deborah A
O'Connor, George
Ober, Carole
Ong, Peck Y
Ortega, Victor E
Paller, Amy S
Putcha, Nirupama
Reed, Robert M
Schneider, Lynda C
Silverman, Edwin K
Slifka, Mark K
Spergel, Jonathan M
Vasan, Ramachandran S
Viaud-Martinez, Karine A
Watson, Harold
Weiss, Scott T
Ruczinski, Ingo
Beaty, Terri H
Mathias, Rasika A
Barnes, Kathleen C
Date
2021-09-15Journal
Journal of Allergy and Clinical ImmunologyPublisher
Elsevier Inc.Type
Article
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Show full item recordAbstract
Background: Total serum IgE (tIgE) is an important intermediate phenotype of allergic disease. Whole genome genetic association studies across ancestries may identify important determinants of IgE. Objective: By leveraging data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) and the Atopic Dermatitis Research Network (ADRN), we aim to increase understanding of genetic variants affecting tIgE production across the ancestry and allergic disease spectrum (N=21,901). Methods: We performed genome-wide association within strata of study, disease, and ancestry groups, and combined results via a meta-regression approach that models heterogeneity attributable to ancestry. We also tested for association between HLA alleles called from whole genome sequence data and tIgE, assessing replication of associations in HLA alleles called from genotype array data. For details, please see the Methods section in this article's Online Repository at www.jacionline.org. Results: We identified six loci at genome-wide significance (P<5x10-9), including four loci previously reported as genome-wide significant for tIgE, as well as new regions in chr11q13.5 and chr15q22.2, also identified in prior GWAS of atopic dermatitis and asthma. In the HLA allele association study, HLA-A*02:01 was associated with decreased tIgE (discovery P = 2x10-4, replication P = 5x10-4, discovery+replication P=4x10-7) and HLA-DQB1*03:02 was strongly associated with decreased tIgE in Hispanic/Latino ancestry populations (Hispanic/Latino discovery+replication P=8x10-8). Conclusion: We performed the largest GWAS and HLA association study of tIgE focused on ancestrally diverse populations and found several known tIgE and allergic disease loci that are relevant in non-European ancestry populations.Rights/Terms
Copyright © 2021. Published by Elsevier Inc.Keyword
asthmaatopic dermatitis
genome-wide association study
human leukocyte antigen
multi-ethnic
total serum IgE
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http://hdl.handle.net/10713/16709ae974a485f413a2113503eed53cd6c53
10.1016/j.jaci.2021.09.011
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