• Maria Pino-Yanes, Christopher R Gignoux, Joshua M Galanter, Albert M Levin, Catarina D Campbell, Celeste Eng, Scott Huntsman, Katherine K Nishimura, Pierre-Antoine Gourraud, Kiana Mohajeri, Brian J O'Roak, Donglei Hu, Rasika A Mathias, Elizabeth A Nguyen, Lindsey A Roth, Badri Padhukasahasram, Andres Moreno-Estrada, Karla Sandoval, Cheryl A Winkler, Fred Lurmann, Adam Davis, Harold J Farber, Kelley Meade, Pedro C Avila, Denise Serebrisky, Rocio Chapela, Jean G Ford, Michael A Lenoir, Shannon M Thyne, Emerita Brigino-Buenaventura, Luisa N Borrell, William Rodriguez-Cintron, Saunak Sen, Rajesh Kumar, Jose R Rodriguez-Santana, Carlos D Bustamante, Fernando D Martinez, Benjamin A Raby, Scott T Weiss, Dan L Nicolae, Carole Ober, Deborah A Meyers, Eugene R Bleecker, Steven J Mack, Ryan D Hernandez, Evan E Eichler, Kathleen C Barnes, L Keoki Williams, Dara G Torgerson, and Esteban G Burchard.
• 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.
• J. Allergy Clin. Immunol. 2015 Jun 1;135(6):1502-10.

BackgroundIgE is a key mediator of allergic inflammation, and its levels are frequently increased in patients with allergic disorders.ObjectiveWe sought to identify genetic variants associated with IgE levels in Latinos.MethodsWe 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.ResultsWe 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).ConclusionWe 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.Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.

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