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