title: A meta-analysis of genome-wide association studies for serum total IgE in diverse study populations.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Albert M
authors.initials: AM
authors.lastname: Levin
authors.forename: Rasika A
authors.initials: RA
authors.lastname: Mathias
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Roth
authors.forename: Denise
authors.initials: D
authors.lastname: Daley
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Myers
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Himes
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Mao
authors.initials: M
authors.lastname: Yang
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.forename: Julie E
authors.initials: JE
authors.lastname: Park
authors.forename: Karla
authors.initials: K
authors.lastname: Zoratti
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Gignoux
authors.forename: Dara G
authors.initials: DG
authors.lastname: Torgerson
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Galanter
authors.forename: Scott
authors.initials: S
authors.lastname: Huntsman
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Nguyen
authors.forename: Allan B
authors.initials: AB
authors.lastname: Becker
authors.forename: Moira
authors.initials: M
authors.lastname: Chan-Yeung
authors.forename: Anita L
authors.initials: AL
authors.lastname: Kozyrskyj
authors.forename: Pui-Yan
authors.initials: PY
authors.lastname: Kwok
authors.forename: Frank D
authors.initials: FD
authors.lastname: Gilliland
authors.forename: W James
authors.initials: WJ
authors.lastname: Gauderman
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Bleecker
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Raby
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Meyers
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Martinez
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.forename: Dan L
authors.initials: DL
authors.lastname: Nicolae
authors.forename: Carole
authors.initials: C
authors.lastname: Ober
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Barnes
authors.forename: L Keoki
authors.initials: LK
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000097:blood / Q000208:ethnology* / Q000235:genetics* / Q000276:immunology; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D055106:Genome-Wide Association Study; D059866:HLA-DQ beta-Chains / Q000097:blood / Q000235:genetics* / Q000276:immunology; D006630:Hispanic or Latino; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014481:United States / Q000453:epidemiology; D044465:White People
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007073:Immunoglobulin E