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

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 & 30 others 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, Esteban G. Burchard

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1502-1510
Number of pages9
JournalJournal of Allergy and Clinical Immunology
Volume135
Issue number6
DOIs
StatePublished - Jun 1 2015

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Genome-Wide Association Study
Hispanic Americans
Immunoglobulin E
African Americans
North American Indians
Zinc Fingers
Single Nucleotide Polymorphism
Genome
Genes
Inflammation Mediators
Proteins
Population

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Pino-Yanes, M., Gignoux, C. R., Galanter, J. M., Levin, A. M., Campbell, C. D., Eng, C., ... Burchard, E. G. (2015). Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos. Journal of Allergy and Clinical Immunology, 135(6), 1502-1510. https://doi.org/10.1016/j.jaci.2014.10.033

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

In: Journal of Allergy and Clinical Immunology, Vol. 135, No. 6, 01.06.2015, p. 1502-1510.

Research output: Contribution to journalArticle

Pino-Yanes, M, Gignoux, CR, Galanter, JM, Levin, AM, Campbell, CD, Eng, C, Huntsman, S, Nishimura, KK, Gourraud, PA, Mohajeri, K, O'Roak, BJ, Hu, D, Mathias, RA, Nguyen, EA, Roth, LA, Padhukasahasram, B, Moreno-Estrada, A, Sandoval, K, Winkler, CA, Lurmann, F, Davis, A, Farber, HJ, Meade, K, Avila, PC, Serebrisky, D, Chapela, R, Ford, JG, Lenoir, MA, Thyne, SM, Brigino-Buenaventura, E, Borrell, LN, Rodriguez-Cintron, W, Sen, S, Kumar, R, Rodriguez-Santana, JR, Bustamante, CD, Martinez, FD, Raby, BA, Weiss, ST, Nicolae, DL, Ober, C, Meyers, DA, Bleecker, ER, Mack, SJ, Hernandez, RD, Eichler, EE, Barnes, KC, Williams, LK, Torgerson, DG & Burchard, EG 2015, 'Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos', Journal of Allergy and Clinical Immunology, vol. 135, no. 6, pp. 1502-1510. https://doi.org/10.1016/j.jaci.2014.10.033
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. / Genome-wide association study and admixture mapping reveal new loci associated with total IgE levels in Latinos. In: Journal of Allergy and Clinical Immunology. 2015 ; Vol. 135, No. 6. pp. 1502-1510.
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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.",
author = "Maria Pino-Yanes and Gignoux, {Christopher R.} and Galanter, {Joshua M.} and Levin, {Albert M.} and Campbell, {Catarina D.} and Celeste Eng and Scott Huntsman and Nishimura, {Katherine K.} and Gourraud, {Pierre Antoine} and Kiana Mohajeri and O'Roak, {Brian J.} and Donglei Hu and Mathias, {Rasika A.} and Nguyen, {Elizabeth A.} and Roth, {Lindsey A.} and Badri Padhukasahasram and Andres Moreno-Estrada and Karla Sandoval and Winkler, {Cheryl A.} and Fred Lurmann and Adam Davis and Farber, {Harold J.} and Kelley Meade and Avila, {Pedro C.} and Denise Serebrisky and Rocio Chapela and Ford, {Jean G.} and Lenoir, {Michael A.} and Thyne, {Shannon M.} and Emerita Brigino-Buenaventura and Borrell, {Luisa N.} and William Rodriguez-Cintron and Saunak Sen and Rajesh Kumar and Rodriguez-Santana, {Jose R.} and Bustamante, {Carlos D.} and Martinez, {Fernando D.} and Raby, {Benjamin A.} and Weiss, {Scott T.} and Nicolae, {Dan L.} and Carole Ober and Meyers, {Deborah A.} and Bleecker, {Eugene R.} and Mack, {Steven J.} and Hernandez, {Ryan D.} and Eichler, {Evan E.} and Barnes, {Kathleen C.} and Williams, {L. Keoki} and Torgerson, {Dara G.} and Burchard, {Esteban G.}",
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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.

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.

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