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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:135

Article

Pino-Yanes, Maria^1,4  Gignoux, Christopher R.^1,2,5  Galanter, Joshua M.^1,2  Levin, Albert M.⁶  Campbell, Catarina D.⁹  Eng, Celeste¹  Huntsman, Scott¹  Nishimura, Katherine K.¹  Gourraud, Pierre-Antoine¹⁰  Mohajeri, Kiana⁹  O'Roak, Brian J.^9,11  Hu, Donglei¹  Mathias, Rasika A.¹²  Nguyen, Elizabeth A.¹  Roth, Lindsey A.¹  Padhukasahasram, Badri⁷  Moreno-Estrada, Andres⁵  Sandoval, Karla⁵  Winkler, Cheryl A.¹³  Lurmann, Fred¹⁴  Davis, Adam¹⁵  Farber, Harold J.^16,17  Meade, Kelley¹⁵  Avila, Pedro C.¹⁸  Serebrisky, Denise²⁰  Chapela, Rocio²¹  Ford, Jean G.²²  Lenoir, Michael A.²³  Thyne, Shannon M.²⁴  Brigino-Buenaventura, Emerita²⁵  Borrell, Luisa N.²⁶  Rodriguez-Cintron, William²⁷  Sen, Saunak³  Kumar, Rajesh¹⁹  Rodriguez-Santana, Jose R.²⁸  Bustamante, Carlos D.⁵  Martinez, Fernando D.^29,30  Raby, Benjamin A.³¹  Weiss, Scott T.³¹  Nicolae, Dan L.³²  Ober, Carole³²  Meyers, Deborah A.³³  Bleecker, Eugene R.³³  Mack, Steven J.³⁴  Hernandez, Ryan D.²  Eichler, Evan E.^9,35  Barnes, Kathleen C.¹²  Williams, L. Keoki^7,8  Torgerson, Dara G.¹  Burchard, Esteban G.^1,2 

[1] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[4] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain

[5] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA

[6] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA

[7] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA

[8] Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI USA

[9] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[10] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA

[11] Oregon Hlth & Sci Univ, Mol & Med Genet Dept, Portland, OR 97201 USA

[12] Johns Hopkins Univ, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD USA

[13] NCI, Basic Res Lab, Ctr Canc Res, Leidos Biomed,Frederick Natl Lab Canc Res, Frederick, MD 21701 USA

[14] Sonoma Technol, Petaluma, NC USA

[15] Childrens Hosp & Res Ctr Oakland, Houston, TX USA

[16] Baylor Coll Med, Dept Pediat, Sect Pulmonol, Houston, TX 77030 USA

[17] Texas Childrens Hosp, Houston, TX 77030 USA

[18] Northwestern Univ, Dept Med, Chicago, IL 60611 USA

[19] Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA

[20] Jacobi Med Ctr, Pediat Pulm Div, Bronx, NY USA

[21] INER, Mexico City, DF, Mexico

[22] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[23] Bay Area Pediat, Oakland, CA USA

[24] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Pediat, San Francisco, CA 94143 USA

[25] Kaiser Permanente Vallejo Med Ctr, Dept Allergy & Immunol, Vallejo, CA USA

[26] CUNY, Grad Program Publ Hlth, Dept Hlth Sci, Bronx, NY USA

[27] Vet Caribbean Hlth Care Syst, San Juan, PR USA

[28] Ctr Neumol Pediat, San Juan, PR USA

[29] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA

[30] Univ Arizona, Inst BIO5, Tucson, AZ USA

[31] Harvard Univ, Brigham & Womens Hosp, Sch Med, Charming Div Network Med,Dept Med, Boston, MA 02115 USA

[32] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[33] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA

[34] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA

[35] Howard Hughes Med Inst, Seattle, WA USA

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

DOI  :  10.1016/j.jaci.2014.10.033

来源: Elsevier

【 摘 要 】

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 x 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 x 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 x 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.

【 授权许可】

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