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Meta-Analysis
. 2011 Jul 31;43(9):887-92.
doi: 10.1038/ng.888.

Meta-analysis of Genome-Wide Association Studies of Asthma in Ethnically Diverse North American Populations

Dara G Torgerson  1 Elizabeth J AmplefordGrace Y ChiuW James GaudermanChristopher R GignouxPenelope E GravesBlanca E HimesAlbert M LevinRasika A MathiasDana B HancockJames W BaurleyCeleste EngDebra A SternJuan C CeledónNicholas RafaelsDaniel CapursoDavid V ContiLindsey A RothManuel Soto-QuirosAlkis TogiasXingnan LiRachel A MyersIsabelle RomieuDavid J Van Den BergDonglei HuNadia N HanselRyan D HernandezElliott IsraelMuhammad T SalamJoshua GalanterPedro C AvilaLydiana AvilaJose R Rodriquez-SantanaRocio ChapelaWilliam Rodriguez-CintronGregory B DietteN Franklin AdkinsonRebekah A AbelKevin D RossMin ShiMezbah U FaruqueGeorgia M DunstonHarold R WatsonVito J ManteseSerpil C EzurumLiming LiangIngo RuczinskiJean G FordScott HuntsmanKian Fan ChungHita VoraXia LiWilliam J CalhounMario CastroJuan J Sienra-MongeBlanca del Rio-NavarroKlaus A DeichmannAndrea HeinzmannSally E WenzelWilliam W BusseJames E GernRobert F Lemanske JrTerri H BeatyEugene R BleeckerBenjamin A RabyDeborah A MeyersStephanie J LondonMexico City Childhood Asthma Study (MCAAS)Frank D GillilandChildren's Health Study (CHS) and HARBORS studyEsteban G BurchardGenetics of Asthma in Latino Americans (GALA) Study, Study of Genes-Environment and Admixture in Latino Americans (GALA2) and Study of African Americans, Asthma, Genes & Environments (SAGE)Fernando D MartinezChildhood Asthma Research and Education (CARE) NetworkScott T WeissChildhood Asthma Management Program (CAMP)L Keoki WilliamsStudy of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE)Kathleen C BarnesGenetic Research on Asthma in African Diaspora (GRAAD) StudyCarole OberDan L Nicolae
Affiliations
Free PMC article
Meta-Analysis

Meta-analysis of Genome-Wide Association Studies of Asthma in Ethnically Diverse North American Populations

Dara G Torgerson et al. Nat Genet. .
Free PMC article

Abstract

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.

Figures

Figure 1
Figure 1. Results of Meta-Analysis on the Chromosome 1 Region of Association in African Americans/African Caribbeans
The relative location of the PYHIN1 gene and direction of transcription are shown in the lower portion of the figure, and the chromosomal position on the x-axis. The light blue line shows the recombination rate across the region (right y-axis), and the left y-axis shows the significance of the associations. The large red diamond shows the p-value for rs1102000. The small diamonds in show the p-values for all other SNPs, color-coded according to the level of LD with rs1102000 in the HapMap YRI (red, r2 > 0.9; orange, r2 = 0.7–0.9; yellow, r2 = 0.5–0.7). Results for the European American, Latino, and combined meta-analysis are shown in Supplementary Fig. 6 online.

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