A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations - 30/03/13
, Rasika A. Mathias, ScD b, c, , Lili Huang, MPH c, Lindsey A. Roth, MA d, Denise Daley, PhD e, Rachel A. Myers, PhD f, Blanca E. Himes, PhD g, Isabelle Romieu, MD, ScD h, Mao Yang, MS i, Celeste Eng, BS d, Julie E. Park, MMath j, Karla Zoratti i, Christopher R. Gignoux, MS d, Dara G. Torgerson, PhD d, Joshua M. Galanter, MD d, Scott Huntsman, MS d, Elizabeth A. Nguyen, BS d, Allan B. Becker, MD k, Moira Chan-Yeung, MD l, Anita L. Kozyrskyj, PhD m, n, Pui-Yan Kwok, MD, PhD o, p, Frank D. Gilliland, MD, PhD q, W. James Gauderman, PhD q, Eugene R. Bleecker, MD r, Benjamin A. Raby, MD, MPH g, Deborah A. Meyers, PhD r, Stephanie J. London, MD, DrPH s, Fernando D. Martinez, MD t, u, Scott T. Weiss, MD, MS g, Esteban G. Burchard, MD, MPH d, v, Dan L. Nicolae, PhD f, w, Carole Ober, PhD f, Kathleen C. Barnes, PhD c, ⁎, ‡ 
, L. Keoki Williams, MD, MPH i, x, ⁎, ‡ Corresponding author: L. Keoki Williams, MD, MPH, Center for Health Services Research, Henry Ford Health System, 1 Ford Place, 3A, Detroit, MI 4820.Kathleen C. Barnes, PhD, Johns Hopkins Asthma & Allergy Center, 5501 Hopkins Bayview Circle, Room 3A.62, Baltimore, MD 21224.Abstract |
Background |
IgE is both a marker and mediator of allergic inflammation. Despite reported differences in serum total IgE levels by race-ethnicity, African American and Latino subjects have not been well represented in genetic studies of total IgE.
Objective |
We sought to identify the genetic predictors of serum total IgE levels.
Methods |
We used genome-wide association data from 4292 subjects (2469 African Americans, 1564 European Americans, and 259 Latinos) in the EVE Asthma Genetics Consortium. Tests for association were performed within each cohort by race-ethnic group (ie, African American, Latino, and European American) and asthma status. The resulting P values were meta-analyzed, accounting for sample size and direction of effect. Top single nucleotide polymorphism associations from the meta-analysis were reassessed in 6 additional cohorts comprising 5767 subjects.
Results |
We identified 10 unique regions in which the combined association statistic was associated with total serum IgE levels (P < 5.0 × 10−6) and the minor allele frequency was 5% or greater in 2 or more population groups. Variant rs9469220, corresponding to HLA-DQB1, was the single nucleotide polymorphism most significantly associated with serum total IgE levels when assessed in both the replication cohorts and the discovery and replication sets combined (P = .007 and 2.45 × 10−7, respectively). In addition, findings from earlier genome-wide association studies were also validated in the current meta-analysis.
Conclusion |
This meta-analysis independently identified a variant near HLA-DQB1 as a predictor of total serum IgE levels in multiple race-ethnic groups. This study also extends and confirms the findings of earlier genome-wide association analyses in African American and Latino subjects.
Le texte complet de cet article est disponible en PDF.Key words : Meta-analysis, genome-wide association study, total IgE, race-ethnicity, continental population groups
Abbreviations used : CAG, CAMP, CARE, CHF, COPD, CSGA, GALA I, GALA II, GRAAD, GWAS, LD, SAGE, SAPPHIRE, SARP, SNP
Plan
| 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. |
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| 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. |
Vol 131 - N° 4
P. 1176-1184 - avril 2013 Retour au numéro
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