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dc.contributor.authorDaya, Michelle
dc.contributor.authorCox, Corey
dc.contributor.authorAcevedo, Nathalie
dc.contributor.authorBoorgula, Meher P
dc.contributor.authorCampbell, Monica
dc.contributor.authorChavan, Sameer
dc.contributor.authorCho, Michael H
dc.contributor.authorDavid, Gloria L
dc.contributor.authorKachroo, Priyadarshini
dc.contributor.authorLasky-Su, Jessica
dc.contributor.authorLi, Xingnan
dc.contributor.authorMcHugh, Caitlin P
dc.contributor.authorQiao, Dandi
dc.contributor.authorRafaels, Nicholas
dc.contributor.authorBeck, Lisa A
dc.contributor.authorBleecker, Eugene R
dc.contributor.authorCaraballo, Luis
dc.contributor.authorCupples, Adrienne L
dc.contributor.authorFigueiredo, Camila A
dc.contributor.authorGallo, Richard L
dc.contributor.authorHanifin, Jon
dc.contributor.authorHansel, Nadia N
dc.contributor.authorHata, Tissa R
dc.contributor.authorHersh, Craig P
dc.contributor.authorKnight-Madden, Jennifer
dc.contributor.authorLeung, Donald Y M
dc.contributor.authorGuttman-Yassky, Emma
dc.contributor.authorMeyers, Deborah A
dc.contributor.authorO'Connor, George
dc.contributor.authorOber, Carole
dc.contributor.authorOng, Peck Y
dc.contributor.authorOrtega, Victor E
dc.contributor.authorPaller, Amy S
dc.contributor.authorPutcha, Nirupama
dc.contributor.authorReed, Robert M
dc.contributor.authorSchneider, Lynda C
dc.contributor.authorSilverman, Edwin K
dc.contributor.authorSlifka, Mark K
dc.contributor.authorSpergel, Jonathan M
dc.contributor.authorVasan, Ramachandran S
dc.contributor.authorViaud-Martinez, Karine A
dc.contributor.authorWatson, Harold
dc.contributor.authorWeiss, Scott T
dc.contributor.authorRuczinski, Ingo
dc.contributor.authorBeaty, Terri H
dc.contributor.authorMathias, Rasika A
dc.contributor.authorBarnes, Kathleen C
dc.date.accessioned2021-09-24T14:46:42Z
dc.date.available2021-09-24T14:46:42Z
dc.date.issued2021-09-15
dc.identifier.urihttp://hdl.handle.net/10713/16709
dc.description.abstractBackground: 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.en_US
dc.description.urihttps://doi.org/10.1016/j.jaci.2021.09.011en_US
dc.language.isoenen_US
dc.publisherElsevier Inc.en_US
dc.relation.ispartofJournal of Allergy and Clinical Immunologyen_US
dc.rightsCopyright © 2021. Published by Elsevier Inc.en_US
dc.subjectasthmaen_US
dc.subjectatopic dermatitisen_US
dc.subjectgenome-wide association studyen_US
dc.subjecthuman leukocyte antigenen_US
dc.subjectmulti-ethnicen_US
dc.subjecttotal serum IgEen_US
dc.titleMulti-ethnic genome-wide and HLA association study of total serum IgEen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.jaci.2021.09.011
dc.identifier.pmid34536413
dc.source.countryUnited States


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