A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations

Albert M. Levin, Rasika A. Mathias, Lili Huang, Lindsey A. Roth, Denise Daley, Rachel A. Myers, Blanca E. Himes, Isabelle Romieu, Mao Yang, Celeste Eng, Julie E. Park, Karla Zoratti, Christopher R. Gignoux, Dara G. Torgerson, Joshua M. Galanter, Scott Huntsman, Elizabeth A. Nguyen, Allan B. Becker, Moira Chan-Yeung, Anita L. KozyrskyjPui Yan Kwok, Frank D. Gilliland, W. James Gauderman, Eugene R. Bleecker, Benjamin A. Raby, Deborah A. Meyers, Stephanie J. London, Fernando D. Martinez, Scott T. Weiss, Esteban G. Burchard, Dan L. Nicolae, Carole Ober, Kathleen C. Barnes, L. Keoki Williams

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1176-1184
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Issue number4
StatePublished - Apr 2013


  • Meta-analysis
  • continental population groups
  • genome-wide association study
  • race-ethnicity
  • total IgE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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