Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: The Genes-environments & Admixture in Latino Americans study

Joshua M. Galanter, Christopher R. Gignoux, Dara G. Torgerson, Lindsey A. Roth, Celeste Eng, Sam S. Oh, Elizabeth A. Nguyen, Katherine A. Drake, Scott Huntsman, Donglei Hu, Saunak Sen, Adam Davis, Harold J. Farber, Pedro C. Avila, Emerita Brigino-Buenaventura, Michael A. Lenoir, Kelley Meade, Denise Serebrisky, Luisa N. Borrell, William Rodríguez-CintrónAndres Moreno Estrada, Karla Sandoval Mendoza, Cheryl A. Winkler, William Klitz, Isabelle Romieu, Stephanie J. London, Frank Gilliland, Fernando Martinez, Carlos Bustamante, L. Keoki Williams, Rajesh Kumar, José R. Rodríguez-Santana, Esteban G. Burchard

Research output: Contribution to journalArticle

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Abstract

Background Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent. Objective We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10-6). This association replicates in a meta-analysis of the EVE Asthma Consortium (P =.01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10-13) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21.

Original languageEnglish (US)
Pages (from-to)295-305
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number2
DOIs
StatePublished - 2014

Fingerprint

Genome-Wide Association Study
Hispanic Americans
Asthma
Genes
Meta-Analysis
Genome
Population
Puerto Rico
San Francisco
Chromosome Mapping
Single Nucleotide Polymorphism
Healthy Volunteers
Odds Ratio

Keywords

  • 17q21
  • 6p21
  • admixture mapping
  • Asthma
  • genome-wide association study
  • Latinos
  • local ancestry

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Medicine(all)

Cite this

Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos : The Genes-environments & Admixture in Latino Americans study. / Galanter, Joshua M.; Gignoux, Christopher R.; Torgerson, Dara G.; Roth, Lindsey A.; Eng, Celeste; Oh, Sam S.; Nguyen, Elizabeth A.; Drake, Katherine A.; Huntsman, Scott; Hu, Donglei; Sen, Saunak; Davis, Adam; Farber, Harold J.; Avila, Pedro C.; Brigino-Buenaventura, Emerita; Lenoir, Michael A.; Meade, Kelley; Serebrisky, Denise; Borrell, Luisa N.; Rodríguez-Cintrón, William; Estrada, Andres Moreno; Mendoza, Karla Sandoval; Winkler, Cheryl A.; Klitz, William; Romieu, Isabelle; London, Stephanie J.; Gilliland, Frank; Martinez, Fernando; Bustamante, Carlos; Williams, L. Keoki; Kumar, Rajesh; Rodríguez-Santana, José R.; Burchard, Esteban G.

In: Journal of Allergy and Clinical Immunology, Vol. 134, No. 2, 2014, p. 295-305.

Research output: Contribution to journalArticle

Galanter, JM, Gignoux, CR, Torgerson, DG, Roth, LA, Eng, C, Oh, SS, Nguyen, EA, Drake, KA, Huntsman, S, Hu, D, Sen, S, Davis, A, Farber, HJ, Avila, PC, Brigino-Buenaventura, E, Lenoir, MA, Meade, K, Serebrisky, D, Borrell, LN, Rodríguez-Cintrón, W, Estrada, AM, Mendoza, KS, Winkler, CA, Klitz, W, Romieu, I, London, SJ, Gilliland, F, Martinez, F, Bustamante, C, Williams, LK, Kumar, R, Rodríguez-Santana, JR & Burchard, EG 2014, 'Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: The Genes-environments & Admixture in Latino Americans study', Journal of Allergy and Clinical Immunology, vol. 134, no. 2, pp. 295-305. https://doi.org/10.1016/j.jaci.2013.08.055
Galanter, Joshua M. ; Gignoux, Christopher R. ; Torgerson, Dara G. ; Roth, Lindsey A. ; Eng, Celeste ; Oh, Sam S. ; Nguyen, Elizabeth A. ; Drake, Katherine A. ; Huntsman, Scott ; Hu, Donglei ; Sen, Saunak ; Davis, Adam ; Farber, Harold J. ; Avila, Pedro C. ; Brigino-Buenaventura, Emerita ; Lenoir, Michael A. ; Meade, Kelley ; Serebrisky, Denise ; Borrell, Luisa N. ; Rodríguez-Cintrón, William ; Estrada, Andres Moreno ; Mendoza, Karla Sandoval ; Winkler, Cheryl A. ; Klitz, William ; Romieu, Isabelle ; London, Stephanie J. ; Gilliland, Frank ; Martinez, Fernando ; Bustamante, Carlos ; Williams, L. Keoki ; Kumar, Rajesh ; Rodríguez-Santana, José R. ; Burchard, Esteban G. / Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos : The Genes-environments & Admixture in Latino Americans study. In: Journal of Allergy and Clinical Immunology. 2014 ; Vol. 134, No. 2. pp. 295-305.
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title = "Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos: The Genes-environments & Admixture in Latino Americans study",
abstract = "Background Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent. Objective We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10-6). This association replicates in a meta-analysis of the EVE Asthma Consortium (P =.01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95{\%} CI, 0.61-0.75; P = 6 × 10-13) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21.",
keywords = "17q21, 6p21, admixture mapping, Asthma, genome-wide association study, Latinos, local ancestry",
author = "Galanter, {Joshua M.} and Gignoux, {Christopher R.} and Torgerson, {Dara G.} and Roth, {Lindsey A.} and Celeste Eng and Oh, {Sam S.} and Nguyen, {Elizabeth A.} and Drake, {Katherine A.} and Scott Huntsman and Donglei Hu and Saunak Sen and Adam Davis and Farber, {Harold J.} and Avila, {Pedro C.} and Emerita Brigino-Buenaventura and Lenoir, {Michael A.} and Kelley Meade and Denise Serebrisky and Borrell, {Luisa N.} and William Rodr{\'i}guez-Cintr{\'o}n and Estrada, {Andres Moreno} and Mendoza, {Karla Sandoval} and Winkler, {Cheryl A.} and William Klitz and Isabelle Romieu and London, {Stephanie J.} and Frank Gilliland and Fernando Martinez and Carlos Bustamante and Williams, {L. Keoki} and Rajesh Kumar and Rodr{\'i}guez-Santana, {Jos{\'e} R.} and Burchard, {Esteban G.}",
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TY - JOUR

T1 - Genome-wide association study and admixture mapping identify different asthma-associated loci in Latinos

T2 - The Genes-environments & Admixture in Latino Americans study

AU - Galanter, Joshua M.

AU - Gignoux, Christopher R.

AU - Torgerson, Dara G.

AU - Roth, Lindsey A.

AU - Eng, Celeste

AU - Oh, Sam S.

AU - Nguyen, Elizabeth A.

AU - Drake, Katherine A.

AU - Huntsman, Scott

AU - Hu, Donglei

AU - Sen, Saunak

AU - Davis, Adam

AU - Farber, Harold J.

AU - Avila, Pedro C.

AU - Brigino-Buenaventura, Emerita

AU - Lenoir, Michael A.

AU - Meade, Kelley

AU - Serebrisky, Denise

AU - Borrell, Luisa N.

AU - Rodríguez-Cintrón, William

AU - Estrada, Andres Moreno

AU - Mendoza, Karla Sandoval

AU - Winkler, Cheryl A.

AU - Klitz, William

AU - Romieu, Isabelle

AU - London, Stephanie J.

AU - Gilliland, Frank

AU - Martinez, Fernando

AU - Bustamante, Carlos

AU - Williams, L. Keoki

AU - Kumar, Rajesh

AU - Rodríguez-Santana, José R.

AU - Burchard, Esteban G.

PY - 2014

Y1 - 2014

N2 - Background Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent. Objective We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10-6). This association replicates in a meta-analysis of the EVE Asthma Consortium (P =.01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10-13) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21.

AB - Background Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent. Objective We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping. Methods Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci. Results We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10-6). This association replicates in a meta-analysis of the EVE Asthma Consortium (P =.01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10-13) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies. Conclusions Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21.

KW - 17q21

KW - 6p21

KW - admixture mapping

KW - Asthma

KW - genome-wide association study

KW - Latinos

KW - local ancestry

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