Mechanisms of allergy and clinical immunologyA meta-analysis of genome-wide association studies for serum total IgE in diverse study populations
Section snippets
Study populations
The EVE consortium comprises 9 investigative teams throughout the United States, each with genome-wide association data for asthma from case-control, trio, or extended family studies.16 All of the cohorts represented in the meta-analysis (ie, the discovery set) were part of the EVE consortium, and each of these individual study populations has been described in detail previously.17, 18, 19, 20, 21, 22, 23, 24, 25 These study populations are broadly representative of the major North American
Results
The characteristics of the 6 study groups in the genome-wide meta-analysis of serum total IgE levels are shown in Table I (subjects in the GRAAD study recruited from the United States and the Caribbean are shown separately). These cohorts comprised 4292 study subjects ranging in age from 1 to 84 years. The combined group included 2425 (56.5%) female subjects and 2754 (64.1%) subjects with a history of asthma. The race-ethnic breakdown of the total group included 2469 (57.4%) African American
Discussion
We are aware of 2 GWASs4, 47 and one genome-wide meta-analysis examining genetic variants associated with serum total IgE levels.6 However, to our knowledge, this is the first of such studies to include substantial numbers of participants who are not primarily European in ancestry (ie, African American and Latino subjects).
Our findings confirm the role of variants in the class II MHC region on serum total IgE levels. In particular, we found that a polymorphism, rs9469220, located between
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2024, Journal of Allergy and Clinical ImmunologyAllergy and autoimmunity: Share of genetics and environment
2022, Translational Autoimmunity: Autoimmune Disease Associated with Different Clinical FeaturesMultiethnic genome-wide and HLA association study of total serum IgE level
2021, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Total IgE level is highly elevated in individuals experiencing atopic diseases such as asthma and is considered a risk factor for this disease. Although several tIgE genome-wide association studies (GWASs) have been reported,3-7 these have mostly been limited to European ancestry populations. The largest GWAS to date included 14,745 European ancestry samples,5 and the only multiethnic GWAS to date included 4,292 samples.4
Genome-wide association study of asthma, total IgE, and lung function in a cohort of Peruvian children
2021, Journal of Allergy and Clinical ImmunologyCitation Excerpt :In the GABRIEL consortium which looked at genetic signals for asthma, the SNP with the strongest association, rs9271300, was located in the MHC region between HLA-DRB1 and HLA-DQA1.46 Similarly, in the EVE Asthma Genetics Consortium, which had better representation of Latino and African American participants, HLA-DRB1 had the strongest association with total serum IgE levels.40 The MHC region contains immune-regulating genes, including HLA-DR-B1 variants, which modulate antigen presentation to TH cells, leading to TH2 skewing.50
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Supported by grants from the National Heart, Lung, and Blood Institute (HL101651 to C.O. and D.L.N.; HL087665 to D.L.N.; HL085197, HL087665, HL072414, and HL49596 to C.O.; HL064307 and HL064313 to F.D.M.; HL075419, HL65899, HL083069, HL066289, HL087680, HL101543, and HL101651 to S.T.W.; HL079055 to L.K.W.; HL087699, HL049612, HL075417, HL04266, and HL072433 to K.C.B.; HL061768, HL076647, to F.D.G.; HL087680 to W.J.G.; HL078885 and HL088133 to E.G.B.; HL087665 to D.A.M.; and HL069167 to E.R.B), the National Institutes of Allergy and Infectious Disease (AI070503 to C.O.; AI079139 and AI061774 to L.K.W.; AI050024, AI044840, and AI041040 to K.C.B.; and AI077439 to E.G.B.), the National Institute of Diabetes and Digestive and Kidney Diseases to L.K.W. (DK064695); the National Institutes of Environmental Health Sciences (ES09606, ES018176, and ES015903 to K.C.B.; ES007048, ES009581, R826708, RD831861, and ES011627 to F.D.G.; ES015794 to E.G.B.; and the Division of Intramural Research, Z01 ES049019, to S.J.L.); the National Center for Research Resources (RR03048 to K.C.B.), the Environmental Protection Agency (83213901 and R-826724 to K.C.B.), the American Asthma Foundation and the Fund for Henry Ford Hospital (to L.K.W.), Mary Beryl Patch Turnbull Scholar Program (to K.C.B.), the National Council of Science and Technology (Mexico; 26206-M to I.R.), the Centers for Disease Control, US (to I.R.); and the Flight Attendant Medical Research Institute (FAMRI), RWJF Amos Medical Faculty Development Award, the American Asthma Foundation, and the Sandler Foundation (to E.G.B.). The Canadian studies (SAGE and CAPPS) were supported by AllerGen NCE (the Allergy, Genes and Environment Network, which is a member of the Networks of Centres of Excellence) and by a grant from the Canadian Institutes for Health Research. D.D. is supported by a Tier II Canadian Research Chair and a scholar award from the Michael Smith Foundation for Health Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Disclosure of potential conflict of interest: A. M. Levin has received grants and travel support from and is employed by the Henry Ford Health System. L. Huang has received grants from the National Institutes of Health (NIH). L. A. Roth has received grants from the NIH. D. Daley has received grants from the Canadian Institutes for Health Research and AllerGen NCE. C. R. Gignoux has stock/stock options with 23andMe, Inc. J. M. Galanter has received grants from the University of California San Francisco and the NIH. S. Huntsman has received grants from the NIH. F. D. Martinez has consultant arrangements with MedImmune, has received grants from the NIH, and has received payment for lectures and travel support from Abbott and Merck. K. C. Barnes has received grants from the NIH; is a member of the board for Genentech; has consultant arrangements with Sanofi-Aventis and Siriur Genomics; is employed by Johns Hopkins University; and has received payment for lectures from the “Evolution and Diseases of Modern Environments” symposium, the Cincinnati CHMC Allergy Conference, the 50th Annual Swineford Allergy Conference, and the American Academy of Allergy, Asthma, & Immunology. L. K. Williams has received grant support from the National Institute of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases and has received payment for lectures from Merck & Co. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors shared first authorship.
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These authors shared senior authorship.