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 - 2014/8
Y1 - 2014/8
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 - Asthma
KW - Latinos
KW - admixture mapping
KW - genome-wide association study
KW - local ancestry
UR - http://www.scopus.com/inward/record.url?scp=84905595372&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905595372&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2013.08.055
DO - 10.1016/j.jaci.2013.08.055
M3 - Article
C2 - 24406073
AN - SCOPUS:84905595372
VL - 134
SP - 295
EP - 305
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 2
ER -