TY - JOUR
T1 - Cosmopolitan and ethnic-specific replication of genetic risk factors for asthma in 2 Latino populations
AU - Galanter, Joshua M.
AU - Torgerson, Dara
AU - Gignoux, Christopher R.
AU - Sen, Saunak
AU - Roth, Lindsey A.
AU - Via, Marc
AU - Aldrich, Melinda C.
AU - Eng, Celeste
AU - Huntsman, Scott
AU - Rodriguez-Santana, Jose
AU - Rodriguez-Cintrón, William
AU - Chapela, Rocio
AU - Ford, Jean G.
AU - Burchard, Esteban G.
N1 - Funding Information:
Supported by the National Institutes of Health ( 2T32GM007546, 1RC2 HL101651, ES015794, U19 AI077439, HL088133, and HL078885 ) and the Flight Attendant Medical Research Institute (FAMRI).
PY - 2011/7
Y1 - 2011/7
N2 - Background: Although Mexicans and Puerto Ricans are jointly classified as "Hispanic/Latino," there are significant differences in asthma prevalence, severity, and mortality between the 2 groups. We sought to examine the possibility that population-specific genetic risks contribute to this disparity. Objectives: More than 100 candidate genes have been associated with asthma and replicated in an independent population, and 7 genome-wide association studies in asthma have been performed. We compared the pattern of replication of these associations in Puerto Ricans and Mexicans. Methods: We genotyped Mexican and Puerto Rican trios using an Affymetrix 6.0 GeneChip and used a family-based analysis to test for genetic associations in 124 genes previously associated with asthma. Results: We identified 32 single nucleotide polymorphisms (SNPs) in 17 genes associated with asthma in at least 1 of the 2 populations. Twenty-two of these SNPs in 11 genes were significantly associated with asthma in the combined population and showed no significant heterogeneity of association, whereas 5 SNPs were associated in only 1 population and showed statistically significant heterogeneity. In a gene-based approach 2 additional genes were associated with asthma in the combined population, and 3 additional genes displayed ethnic-specific associations with heterogeneity. Conclusions: Our results show that only a minority of genetic association studies replicate in our population of Mexican and Puerto Rican asthmatic subjects. Among SNPs that were successfully replicated, most showed no significant heterogeneity across populations. However, we identified several population-specific genetic associations.
AB - Background: Although Mexicans and Puerto Ricans are jointly classified as "Hispanic/Latino," there are significant differences in asthma prevalence, severity, and mortality between the 2 groups. We sought to examine the possibility that population-specific genetic risks contribute to this disparity. Objectives: More than 100 candidate genes have been associated with asthma and replicated in an independent population, and 7 genome-wide association studies in asthma have been performed. We compared the pattern of replication of these associations in Puerto Ricans and Mexicans. Methods: We genotyped Mexican and Puerto Rican trios using an Affymetrix 6.0 GeneChip and used a family-based analysis to test for genetic associations in 124 genes previously associated with asthma. Results: We identified 32 single nucleotide polymorphisms (SNPs) in 17 genes associated with asthma in at least 1 of the 2 populations. Twenty-two of these SNPs in 11 genes were significantly associated with asthma in the combined population and showed no significant heterogeneity of association, whereas 5 SNPs were associated in only 1 population and showed statistically significant heterogeneity. In a gene-based approach 2 additional genes were associated with asthma in the combined population, and 3 additional genes displayed ethnic-specific associations with heterogeneity. Conclusions: Our results show that only a minority of genetic association studies replicate in our population of Mexican and Puerto Rican asthmatic subjects. Among SNPs that were successfully replicated, most showed no significant heterogeneity across populations. However, we identified several population-specific genetic associations.
KW - Asthma
KW - Hispanics
KW - Latinos
KW - Mexicans
KW - Puerto Ricans
KW - candidate genes
KW - effect heterogeneity
KW - genetics
KW - genome-wide association
KW - replication
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U2 - 10.1016/j.jaci.2011.03.050
DO - 10.1016/j.jaci.2011.03.050
M3 - Article
C2 - 21621256
AN - SCOPUS:80955177163
SN - 0091-6749
VL - 128
SP - 37-43.e12
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 1
ER -