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Differences in candidate gene association between European ancestry and African American asthmatic children.

Baye TM, Butsch Kovacic M, Biagini Myers JM, Martin LJ, Lindsey M, Patterson TL, He H, Ericksen MB, Gupta J, Tsoras AM, Lindsley A, Rothenberg ME, Wills-Karp M, Eissa NT, Borish L, Khurana Hershey GK - PLoS ONE (2011)

Bottom Line: 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.African ancestry.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.

ABSTRACT

Background: 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.

Methodology/principal findings: 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.

Conclusions/significance: 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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Related in: MedlinePlus

Pair-wise LD statistics.Pairs of common SNPs in genomic regions containing IL4 and IL13 in the Caucasian (A) and African American (B) population. The positions of SNPs within the IL4 and IL13 genes are shown above the plot. Values in boxes are r2 measures on a decimal scale (i.e. 97 represent r2 = 0.97), indicating extent of LD between two SNPs. Box without numbers have r2 = 1. The shade of each square indicates the strength of the LD relationship between pairs of SNPs.
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pone-0016522-g002: Pair-wise LD statistics.Pairs of common SNPs in genomic regions containing IL4 and IL13 in the Caucasian (A) and African American (B) population. The positions of SNPs within the IL4 and IL13 genes are shown above the plot. Values in boxes are r2 measures on a decimal scale (i.e. 97 represent r2 = 0.97), indicating extent of LD between two SNPs. Box without numbers have r2 = 1. The shade of each square indicates the strength of the LD relationship between pairs of SNPs.

Mentions: To investigate if the strong single SNP association of IL4 gene is independent of IL13, linkage disequilibrium (LD) analyses were performed. IL13 is an adjacent cytokine gene, which lies 200 kb away from IL4 on chromosome 5q31 and has many structural and functional similarities with IL4 including a shared receptor (IL4Rα). All the genotyped IL4 SNPs in Caucasians and African Americans were studied for LD patterns. In both populations, LD within the IL4 gene was strong. However, LD was not observed between IL13 and IL4 in the African American population, while weak LD was observed between IL13 and IL4 genes in Caucasians (Figure 2). As LD is known to be highly influenced by ancestry, the observed patterns of LD and SNP relationships indicate that these populations are genetically different. There was no significant difference in LD pattern between cases and control subjects in either population (data not shown).


Differences in candidate gene association between European ancestry and African American asthmatic children.

Baye TM, Butsch Kovacic M, Biagini Myers JM, Martin LJ, Lindsey M, Patterson TL, He H, Ericksen MB, Gupta J, Tsoras AM, Lindsley A, Rothenberg ME, Wills-Karp M, Eissa NT, Borish L, Khurana Hershey GK - PLoS ONE (2011)

Pair-wise LD statistics.Pairs of common SNPs in genomic regions containing IL4 and IL13 in the Caucasian (A) and African American (B) population. The positions of SNPs within the IL4 and IL13 genes are shown above the plot. Values in boxes are r2 measures on a decimal scale (i.e. 97 represent r2 = 0.97), indicating extent of LD between two SNPs. Box without numbers have r2 = 1. The shade of each square indicates the strength of the LD relationship between pairs of SNPs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046166&req=5

pone-0016522-g002: Pair-wise LD statistics.Pairs of common SNPs in genomic regions containing IL4 and IL13 in the Caucasian (A) and African American (B) population. The positions of SNPs within the IL4 and IL13 genes are shown above the plot. Values in boxes are r2 measures on a decimal scale (i.e. 97 represent r2 = 0.97), indicating extent of LD between two SNPs. Box without numbers have r2 = 1. The shade of each square indicates the strength of the LD relationship between pairs of SNPs.
Mentions: To investigate if the strong single SNP association of IL4 gene is independent of IL13, linkage disequilibrium (LD) analyses were performed. IL13 is an adjacent cytokine gene, which lies 200 kb away from IL4 on chromosome 5q31 and has many structural and functional similarities with IL4 including a shared receptor (IL4Rα). All the genotyped IL4 SNPs in Caucasians and African Americans were studied for LD patterns. In both populations, LD within the IL4 gene was strong. However, LD was not observed between IL13 and IL4 in the African American population, while weak LD was observed between IL13 and IL4 genes in Caucasians (Figure 2). As LD is known to be highly influenced by ancestry, the observed patterns of LD and SNP relationships indicate that these populations are genetically different. There was no significant difference in LD pattern between cases and control subjects in either population (data not shown).

Bottom Line: 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.African ancestry.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.

ABSTRACT

Background: 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.

Methodology/principal findings: 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.

Conclusions/significance: 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.

Show MeSH
Related in: MedlinePlus