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J Allergy Clin Immunol. 2015 Jun;135(6):1502-10. doi: 10.1016/j.jaci.2014.10.033. Epub 2014 Dec 6.

Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos.

Author information

1
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.
2
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.
3
Department of Medicine, University of California, San Francisco, Calif; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.
4
Department of Public Health Sciences, Henry Ford Health System, Detroit, Mich.
5
Department of Genome Sciences, University of Washington, Seattle, Wash.
6
Department of Medicine, University of California, San Francisco, Calif.
7
Department of Neurology, University of California, San Francisco, Calif.
8
Department of Genome Sciences, University of Washington, Seattle, Wash; Molecular & Medical Genetics Department, Oregon Health and Science University, Portland, Ore.
9
Division of Allergy & Clinical Immunology, Department of Medicine, Johns Hopkins University, Baltimore, Md.
10
Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Mich.
11
Department of Genetics, Stanford University, Palo Alto, Calif.
12
Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Leidos Biomedical, Frederick National Laboratory for Cancer Research, Frederick, Md.
13
Sonoma Technology, Petaluma, Calif.
14
Children's Hospital and Research Center Oakland, Oakland, Calif.
15
Department of Pediatrics, Section of Pulmonology, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex.
16
Department of Medicine, Northwestern University, Chicago, Ill.
17
Pediatric Pulmonary Division, Jacobi Medical Center, Bronx, NY.
18
Instituto Nacional de Enfermedades Respiratorias (INER), Mexico City, Mexico.
19
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md.
20
Bay Area Pediatrics, Oakland, Calif.
21
Department of Pediatrics, University of California San Francisco, San Francisco General Hospital, San Francisco, Calif.
22
Department of Allergy and Immunology, Kaiser Permanente-Vallejo Medical Center, Vallejo, Calif.
23
Department of Health Sciences, Graduate Program in Public Health, City University of New York, Bronx, NY.
24
Veterans Caribbean Health Care System, San Juan, Puerto Rico.
25
Department of Epidemiology and Biostatistics, University of California, San Francisco, Calif.
26
Children's Memorial Hospital and the Feinberg School of Medicine, Northwestern University, Chicago, Ill.
27
Centro de Neumología Pediátrica, San Juan, Puerto Rico.
28
Arizona Respiratory Center, University of Arizona, Tucson, Ariz; BIO5 Institute, University of Arizona, Tucson, Ariz.
29
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
30
Department of Human Genetics, University of Chicago, Chicago, Ill.
31
Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC.
32
Children's Hospital Oakland Research Institute, Oakland, Calif.
33
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, Calif.
34
Department of Genome Sciences, University of Washington, Seattle, Wash; Howard Hughes Medical Institute, Seattle, Wash.
35
Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Mich; Department of Internal Medicine, Henry Ford Health System, Detroit, Mich.

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).

CONCLUSION:

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.

KEYWORDS:

Hispanics; IgE; Latinos; admixture mapping; allergy; asthma; genome-wide association study; minority populations; next-generation sequencing

PMID:
25488688
PMCID:
PMC4458233
DOI:
10.1016/j.jaci.2014.10.033
[Indexed for MEDLINE]
Free PMC Article

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