Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Maria Pino-Yanes  1 , Christopher R Gignoux  2 , Joshua M Galanter  3 , Albert M Levin  4 , Catarina D Campbell  5 , Celeste Eng  6 , Scott Huntsman  6 , Katherine K Nishimura  6 , Pierre-Antoine Gourraud  7 , Kiana Mohajeri  5 , Brian J O'Roak  8 , Donglei Hu  6 , Rasika A Mathias  9 , Elizabeth A Nguyen  6 , Lindsey A Roth  6 , Badri Padhukasahasram  10 , Andres Moreno-Estrada  11 , Karla Sandoval  11 , Cheryl A Winkler  12 , Fred Lurmann  13 , Adam Davis  14 , Harold J Farber  15 , Kelley Meade  14 , Pedro C Avila  16 , Denise Serebrisky  17 , Rocio Chapela  18 , Jean G Ford  19 , Michael A Lenoir  20 , Shannon M Thyne  21 , Emerita Brigino-Buenaventura  22 , Luisa N Borrell  23 , William Rodriguez-Cintron  24 , Saunak Sen  25 , Rajesh Kumar  26 , Jose R Rodriguez-Santana  27 , Carlos D Bustamante  11 , Fernando D Martinez  28 , Benjamin A Raby  29 , Scott T Weiss  29 , Dan L Nicolae  30 , Carole Ober  30 , Deborah A Meyers  31 , Eugene R Bleecker  31 , Steven J Mack  32 , Ryan D Hernandez  33 , Evan E Eichler  34 , Kathleen C Barnes  9 , L Keoki Williams  35 , Dara G Torgerson  6 , Esteban G Burchard  3
Affiliations

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

Maria Pino-Yanes et al. J Allergy Clin Immunol. 2015 Jun.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Fine mapping of ZNF365 in GALA II. Included in the plot are -log10(p-values) of association with total serum IgE by chromosome position. The most significant SNP is represented by a diamond and the results for the remaining SNPs are color coded to show their linkage disequilibrium (LD) with this SNP based on pairwise r2 values from the Latino populations of the 1000 Genomes Project. SNPs above the dashed line are genome-wide significant (p≤5x10−8).
Figure 2
Figure 2
Boxplot showing the distribution of IgE levels for each copy of a chromosome of A) Native American, B) European, and C) African ancestry at 6p21.33.
Figure 3
Figure 3
Fine mapping results of 6p21.32-p22.1 in GALA II, focusing on the region showing genome-wide significant allelic associations. Included in the plot are -log10(p-values) of association with total serum IgE by chromosome position. The most significant SNP is represented by a diamond and the results for the remaining SNPs are color coded to show their linkage disequilibrium (LD) with this SNP based on pairwise r2 values from the Latino populations of the 1000 Genomes Project. SNPs above the dashed line are genome-wide significant (p≤5x10−8).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • What Ancestry Can Tell Us About the Genetic Origins of Inter-Ethnic Differences in Asthma Expression.
    Hernandez-Pacheco N, Flores C, Oh SS, Burchard EG, Pino-Yanes M. Hernandez-Pacheco N, et al. Curr Allergy Asthma Rep. 2016 Jul;16(8):53. doi: 10.1007/s11882-016-0635-4. Curr Allergy Asthma Rep. 2016. PMID: 27393700 Review.
  • From gene identifications to therapeutic targets for asthma: Focus on great potentials of TSLP, ORMDL3, and GSDMB.
    Zhang Y. Zhang Y. Chin Med J Pulm Crit Care Med. 2023 Sep 14;1(3):139-147. doi: 10.1016/j.pccm.2023.08.001. eCollection 2023 Sep. Chin Med J Pulm Crit Care Med. 2023. PMID: 39171126 Free PMC article. Review.
  • LTA4H rs2660845 association with montelukast response in early and late-onset asthma.
    Maroteau C, Espuela-Ortiz A, Herrera-Luis E, Srinivasan S, Carr F, Tavendale R, Wilson K, Hernandez-Pacheco N, Chalmers JD, Turner S, Mukhopadhyay S, Maitland-van der Zee AH, Burchard EG, Pino-Yanes M, Young S, Lassi G, Platt A, Palmer CNA; PiCA Consortium. Maroteau C, et al. PLoS One. 2021 Sep 22;16(9):e0257396. doi: 10.1371/journal.pone.0257396. eCollection 2021. PLoS One. 2021. PMID: 34550981 Free PMC article.
  • Multiethnic genome-wide and HLA association study of total serum IgE level.
    Daya M, Cox C, Acevedo N, Boorgula MP, Campbell M, Chavan S, Cho MH, David GL, Kachroo P, Lasky-Su J, Li X, McHugh CP, Qiao D, Rafaels N, Beck LA, Bleecker ER, Caraballo L, Cupples AL, Figueiredo CA, Gallo RL, Hanifin J, Hansel NN, Hata TR, Hersh CP, Knight-Madden J, Leung DYM, Guttman-Yassky E, Meyers DA, O'Connor G, Ober C, Ong PY, Ortega VE, Paller AS, Putcha N, Reed RM, Schneider LC, Silverman EK, Slifka MK, Spergel JM, Vasan RS, Viaud-Martinez KA, Watson H, Weiss ST; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; Ruczinski I, Beaty TH, Mathias RA, Barnes KC. Daya M, et al. J Allergy Clin Immunol. 2021 Dec;148(6):1589-1595. doi: 10.1016/j.jaci.2021.09.011. Epub 2021 Sep 15. J Allergy Clin Immunol. 2021. PMID: 34536413 Free PMC article.
  • Genetics of Latin American Diversity Project: Insights into population genetics and association studies in admixed groups in the Americas.
    Borda V, Loesch DP, Guo B, Laboulaye R, Veliz-Otani D, French JN, Leal TP, Gogarten SM, Ikpe S, Gouveia MH, Mendes M, Abecasis GR, Alvim I, Arboleda-Bustos CE, Arboleda G, Arboleda H, Barreto ML, Barwick L, Bezzera MA, Blangero J, Borges V, Caceres O, Cai J, Chana-Cuevas P, Chen Z, Custer B, Dean M, Dinardo C, Domingos I, Duggirala R, Dieguez E, Fernandez W, Ferraz HB, Gilliland F, Guio H, Horta B, Curran JE, Johnsen JM, Kaplan RC, Kelly S, Kenny EE, Konkle BA, Kooperberg C, Lescano A, Lima-Costa MF, Loos RJF, Manichaikul A, Meyers DA, Naslavsky MS, Nickerson DA, North KE, Padilla C, Preuss M, Raggio V, Reiner AP, Rich SS, Rieder CR, Rienstra M, Rotter JI, Rundek T, Sacco RL, Sanchez C, Sankaran VG, Santos-Lobato BL, Schumacher-Schuh AF, Scliar MO, Silverman EK, Sofer T, Lasky-Su J, Tumas V, Weiss ST; Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD); National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN) Consortium; Trans-Omics for Precision Medicine (TOPMed) Population Genetics Working Group; Mata IF, Hernandez RD, Tarazona-Santos E, O'Connor TD. Borda V, et al. Cell Genom. 2024 Nov 13;4(11):100692. doi: 10.1016/j.xgen.2024.100692. Epub 2024 Oct 31. Cell Genom. 2024. PMID: 39486408 Free PMC article.
See all "Cited by" articles

References

    1. Weidinger S, Baurecht H, Naumann A, Novak N. Genome-wide association studies on IgE regulation: are genetics of IgE also genetics of atopic disease? Curr Opin Allergy Clin Immunol. 2010;10:408–417. - PubMed
    1. Flohr C, Quinnell RJ, Britton J. Do helminth parasites protect against atopy and allergic disease? Clin Exp Allergy. 2009;39:20–32. - PubMed
    1. Naqvi M, Choudhry S, Tsai HJ, Thyne S, Navarro D, Nazario S, et al. Association between IgE levels and asthma severity among African American, Mexican, and Puerto Rican patients with asthma. J Allergy Clin Immunol. 2007;120:137–143. - PubMed
    1. Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Cioppa GD, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108:184–190. - PubMed
    1. Lanier B, Bridges T, Kulus M, Taylor AF, Berhane I, Vidaurre CF. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009;124:1210–1216. - PubMed

Publication types

Grants and funding