title: Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos.
abstract: BACKGROUND
  IgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders.
  
  
  OBJECTIVE
  We sought to identify genetic variants associated with IgE levels in Latinos.
  
  
  METHODS
  We performed a genome-wide association study and admixture mapping of total IgE levels in 3334 Latinos from the Genes-environments & Admixture in Latino Americans (GALA II) study. Replication was evaluated in 454 Latinos, 1564 European Americans, and 3187 African Americans from independent studies.
  
  
  RESULTS
  We confirmed associations of 6 genes identified by means of previous genome-wide association studies and identified a novel genome-wide significant association of a polymorphism in the zinc finger protein 365 gene (ZNF365) with total IgE levels (rs200076616, P = 2.3 × 10(-8)). We next identified 4 admixture mapping peaks (6p21.32-p22.1, 13p22-31, 14q23.2, and 22q13.1) at which local African, European, and/or Native American ancestry was significantly associated with IgE levels. The most significant peak was 6p21.32-p22.1, where Native American ancestry was associated with lower IgE levels (P = 4.95 × 10(-8)). All but 22q13.1 were replicated in an independent sample of Latinos, and 2 of the peaks were replicated in African Americans (6p21.32-p22.1 and 14q23.2). Fine mapping of 6p21.32-p22.1 identified 6 genome-wide significant single nucleotide polymorphisms in Latinos, 2 of which replicated in European Americans. Another single nucleotide polymorphism was peak-wide significant within 14q23.2 in African Americans (rs1741099, P = 3.7 × 10(-6)) and replicated in non-African American samples (P = .011).
  
  
  CONCLUSIONS
  We confirmed genetic associations at 6 genes and identified novel associations within ZNF365, HLA-DQA1, and 14q23.2. Our results highlight the importance of studying diverse multiethnic populations to uncover novel loci associated with total IgE levels.
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain. Electronic address: mdelpino@ull.edu.es.
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authors.affiliation: Department of Medicine, University of California, San Francisco, Calif; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif; Department of Genetics, Stanford University, Palo Alto, Calif.
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authors.affiliation: Department of Medicine, University of California, San Francisco, Calif; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.
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authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Wash.
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authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
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authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
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authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
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authors.affiliation: Department of Neurology, University of California, San Francisco, Calif.
authors.forename: Pierre-Antoine
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authors.lastname: Gourraud
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Wash.
authors.forename: Kiana
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authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Wash; Molecular & Medical Genetics Department, Oregon Health and Science University, Portland, Ore.
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authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
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authors.affiliation: Division of Allergy & Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, Md.
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authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
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authors.affiliation: Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Mich.
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authors.affiliation: Department of Genetics, Stanford University, Palo Alto, Calif.
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authors.affiliation: Department of Genetics, Stanford University, Palo Alto, Calif.
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authors.affiliation: Department of Allergy and Immunology, Kaiser Permanente-Vallejo Medical Center, Vallejo, Calif.
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authors.affiliation: Department of Health Sciences, Graduate Program in Public Health, City University of New York, Bronx, NY.
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authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, Calif.
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authors.affiliation: Arizona Respiratory Center, University of Arizona, Tucson, Ariz; BIO5 Institute, University of Arizona, Tucson, Ariz.
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authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
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authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
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authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Ill.
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authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Ill.
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authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.
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authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.
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authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, Wash; Howard Hughes Medical Institute, Seattle, Wash.
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authors.affiliation: Division of Allergy & Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, Md.
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authors.affiliation: Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Mich; Department of Internal Medicine, Henry Ford Health System, Detroit, Mich.
authors.forename: L Keoki
authors.initials: LK
authors.lastname: Williams
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif.
authors.forename: Dara G
authors.initials: DG
authors.lastname: Torgerson
authors.affiliation: Department of Medicine, University of California, San Francisco, Calif; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.
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mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D002648:Child; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D006630:Hispanic or Latino; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics; D044465:White People
chemical_list: D004268:DNA-Binding Proteins; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D014157:Transcription Factors; C475725:ZNF365 protein, human; D007073:Immunoglobulin E
keywords: Hispanics; IgE; Latinos; admixture mapping; allergy; asthma; genome-wide association study; minority populations; next-generation sequencing