TY - JOUR
T1 - Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos
AU - Pino-Yanes, Maria
AU - Gignoux, Christopher R.
AU - Galanter, Joshua M.
AU - Levin, Albert M.
AU - Campbell, Catarina D.
AU - Eng, Celeste
AU - Huntsman, Scott
AU - Nishimura, Katherine K.
AU - Gourraud, Pierre Antoine
AU - Mohajeri, Kiana
AU - O'Roak, Brian J.
AU - Hu, Donglei
AU - Mathias, Rasika A.
AU - Nguyen, Elizabeth A.
AU - Roth, Lindsey A.
AU - Padhukasahasram, Badri
AU - Moreno-Estrada, Andres
AU - Sandoval, Karla
AU - Winkler, Cheryl A.
AU - Lurmann, Fred
AU - Davis, Adam
AU - Farber, Harold J.
AU - Meade, Kelley
AU - Avila, Pedro C.
AU - Serebrisky, Denise
AU - Chapela, Rocio
AU - Ford, Jean G.
AU - Lenoir, Michael A.
AU - Thyne, Shannon M.
AU - Brigino-Buenaventura, Emerita
AU - Borrell, Luisa N.
AU - Rodriguez-Cintron, William
AU - Sen, Saunak
AU - Kumar, Rajesh
AU - Rodriguez-Santana, Jose R.
AU - Bustamante, Carlos D.
AU - Martinez, Fernando D.
AU - Raby, Benjamin A.
AU - Weiss, Scott T.
AU - Nicolae, Dan L.
AU - Ober, Carole
AU - Meyers, Deborah A.
AU - Bleecker, Eugene R.
AU - Mack, Steven J.
AU - Hernandez, Ryan D.
AU - Eichler, Evan E.
AU - Barnes, Kathleen C.
AU - Williams, L. Keoki
AU - Torgerson, Dara G.
AU - Burchard, Esteban G.
N1 - Publisher Copyright:
© 2014 American Academy of Allergy, Asthma & Immunology.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
KW - Hispanics
KW - IgE
KW - Latinos
KW - admixture mapping
KW - allergy
KW - asthma
KW - genome-wide association study
KW - minority populations
KW - next-generation sequencing
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U2 - 10.1016/j.jaci.2014.10.033
DO - 10.1016/j.jaci.2014.10.033
M3 - Article
C2 - 25488688
AN - SCOPUS:84941343274
SN - 0091-6749
VL - 135
SP - 1502
EP - 1510
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 6
ER -