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

Albert M. Levin, Rasika 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. Kozyrskyj & 14 others Pui 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 journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1176-1184
Number of pages9
JournalThe Journal of Allergy and Clinical Immunology
Volume131
Issue number4
DOIs
StatePublished - Apr 2013

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Genome-Wide Association Study
Immunoglobulin E
Meta-Analysis
Hispanic Americans
African Americans
Serum
Population
Ethnic Groups
Single Nucleotide Polymorphism
Asthma
Inflammation Mediators
Population Groups
Gene Frequency
Sample Size
Genome

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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

In: The Journal of Allergy and Clinical Immunology, Vol. 131, No. 4, 04.2013, p. 1176-1184.

Research output: Contribution to journalArticle

Levin, AM, Mathias, R, Huang, L, Roth, LA, Daley, D, Myers, RA, Himes, BE, Romieu, I, Yang, M, Eng, C, Park, JE, Zoratti, K, Gignoux, CR, Torgerson, DG, Galanter, JM, Huntsman, S, Nguyen, EA, Becker, AB, Chan-Yeung, M, Kozyrskyj, AL, Kwok, PY, Gilliland, FD, Gauderman, WJ, Bleecker, ER, Raby, BA, Meyers, DA, London, SJ, Martinez, FD, Weiss, ST, Burchard, EG, Nicolae, DL, Ober, C, Barnes, KC & Williams, LK 2013, 'A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations', The Journal of Allergy and Clinical Immunology, vol. 131, no. 4, pp. 1176-1184. https://doi.org/10.1016/j.jaci.2012.10.002
Levin, Albert M. ; Mathias, Rasika ; Huang, Lili ; Roth, Lindsey A. ; Daley, Denise ; Myers, Rachel A. ; Himes, Blanca E. ; Romieu, Isabelle ; Yang, Mao ; Eng, Celeste ; Park, Julie E. ; Zoratti, Karla ; Gignoux, Christopher R. ; Torgerson, Dara G. ; Galanter, Joshua M. ; Huntsman, Scott ; Nguyen, Elizabeth A. ; Becker, Allan B. ; Chan-Yeung, Moira ; Kozyrskyj, Anita L. ; Kwok, Pui Yan ; Gilliland, Frank D. ; Gauderman, W. James ; Bleecker, Eugene R. ; Raby, Benjamin A. ; Meyers, Deborah A. ; London, Stephanie J. ; Martinez, Fernando D. ; Weiss, Scott T. ; Burchard, Esteban G. ; Nicolae, Dan L. ; Ober, Carole ; Barnes, Kathleen C. ; Williams, L. Keoki. / A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations. In: The Journal of Allergy and Clinical Immunology. 2013 ; Vol. 131, No. 4. pp. 1176-1184.
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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.",
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T1 - A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations

AU - Levin, Albert M.

AU - Mathias, Rasika

AU - Huang, Lili

AU - Roth, Lindsey A.

AU - Daley, Denise

AU - Myers, Rachel A.

AU - Himes, Blanca E.

AU - Romieu, Isabelle

AU - Yang, Mao

AU - Eng, Celeste

AU - Park, Julie E.

AU - Zoratti, Karla

AU - Gignoux, Christopher R.

AU - Torgerson, Dara G.

AU - Galanter, Joshua M.

AU - Huntsman, Scott

AU - Nguyen, Elizabeth A.

AU - Becker, Allan B.

AU - Chan-Yeung, Moira

AU - Kozyrskyj, Anita L.

AU - Kwok, Pui Yan

AU - Gilliland, Frank D.

AU - Gauderman, W. James

AU - Bleecker, Eugene R.

AU - Raby, Benjamin A.

AU - Meyers, Deborah A.

AU - London, Stephanie J.

AU - Martinez, Fernando D.

AU - Weiss, Scott T.

AU - Burchard, Esteban G.

AU - Nicolae, Dan L.

AU - Ober, Carole

AU - Barnes, Kathleen C.

AU - Williams, L. Keoki

PY - 2013/4

Y1 - 2013/4

N2 - 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.

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KW - continental population groups

KW - genome-wide association study

KW - Meta-analysis

KW - race-ethnicity

KW - total IgE

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