Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
PLoS ONE (Impact Factor: 3.23). 02/2011; 6(2):e16522. DOI: 10.1371/journal.pone.0016522
Source: PubMed


Candidate gene case-control studies have identified several single nucleotide polymorphisms (SNPs) that are associated with asthma susceptibility. Most of these studies have been restricted to evaluations of specific SNPs within a single gene and within populations from European ancestry. Recently, there is increasing interest in understanding racial differences in genetic risk associated with childhood asthma. Our aim was to compare association patterns of asthma candidate genes between children of European and African ancestry.
Using a custom-designed Illumina SNP array, we genotyped 1,485 children within the Greater Cincinnati Pediatric Clinic Repository and Cincinnati Genomic Control Cohort for 259 SNPs in 28 genes and evaluated their associations with asthma. We identified 14 SNPs located in 6 genes that were significantly associated (p-values <0.05) with childhood asthma in African Americans. Among Caucasians, 13 SNPs in 5 genes were associated with childhood asthma. Two SNPs in IL4 were associated with asthma in both races (p-values <0.05). Gene-gene interaction studies identified race specific sets of genes that best discriminate between asthmatic children and non-allergic controls.
We identified IL4 as having a role in asthma susceptibility in both African American and Caucasian children. However, while IL4 SNPs were associated with asthma in asthmatic children with European and African ancestry, the relative contributions of the most replicated asthma-associated SNPs varied by ancestry. These data provides valuable insights into the pathways that may predispose to asthma in individuals with European vs. African ancestry.

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    • "Furthermore, there is selection bias toward ‘top hits’ in GWAS. As reported by Baye et al. [7], the problem of focusing on few top-hit SNPs is that if the p value threshold is set too low, genes that have little effect individually but are relevant to complex traits when they interact with other genes are not detectable. Recently, Torgerson et al. [8] conducted genetic association studies across asthmatic populations with a cutoff p value of 10−6 and discovered 34 SNPs in European-Americans, 4 SNPs in African-Americans and African-Caribbeans, 32 in the Hispanic-Americans, and 75 in the combined meta-analysis. "
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