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Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP.

Grant SF, Li M, Bradfield JP, Kim CE, Annaiah K, Santa E, Glessner JT, Casalunovo T, Frackelton EC, Otieno FG, Shaner JL, Smith RM, Imielinski M, Eckert AW, Chiavacci RM, Berkowitz RI, Hakonarson H - PLoS ONE (2008)

Bottom Line: We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA).Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA.We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation.

View Article: PubMed Central - PubMed

Affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America. grants@chop.edu

ABSTRACT
Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI>or=95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r(2) = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08-1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91-1.21; P = 0.49) and of 1.31 (95% CI 1.050-1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact.

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Linkage disequilibrium (r2) between SNPs at the FTO locus in (a) Caucasians and (b) African Americans: Plotted are −log10(P-value) of allelic chi-squared tests.The strength of linkage disequilibrium (r2) between SNPs is represented both numerically and by the depth of shading
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pone-0001746-g001: Linkage disequilibrium (r2) between SNPs at the FTO locus in (a) Caucasians and (b) African Americans: Plotted are −log10(P-value) of allelic chi-squared tests.The strength of linkage disequilibrium (r2) between SNPs is represented both numerically and by the depth of shading

Mentions: These results demonstrate the impact of variation at this locus in AA and how we have refined the signal to rs3751812, such that it is closer to the causative underlying mutation (Figure 1). This is as a consequence of LD structural differences between African and Caucasian ancestries, as seen in our cohort (Figure S1) and in the HapMap (Figure S2).


Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP.

Grant SF, Li M, Bradfield JP, Kim CE, Annaiah K, Santa E, Glessner JT, Casalunovo T, Frackelton EC, Otieno FG, Shaner JL, Smith RM, Imielinski M, Eckert AW, Chiavacci RM, Berkowitz RI, Hakonarson H - PLoS ONE (2008)

Linkage disequilibrium (r2) between SNPs at the FTO locus in (a) Caucasians and (b) African Americans: Plotted are −log10(P-value) of allelic chi-squared tests.The strength of linkage disequilibrium (r2) between SNPs is represented both numerically and by the depth of shading
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2262153&req=5

pone-0001746-g001: Linkage disequilibrium (r2) between SNPs at the FTO locus in (a) Caucasians and (b) African Americans: Plotted are −log10(P-value) of allelic chi-squared tests.The strength of linkage disequilibrium (r2) between SNPs is represented both numerically and by the depth of shading
Mentions: These results demonstrate the impact of variation at this locus in AA and how we have refined the signal to rs3751812, such that it is closer to the causative underlying mutation (Figure 1). This is as a consequence of LD structural differences between African and Caucasian ancestries, as seen in our cohort (Figure S1) and in the HapMap (Figure S2).

Bottom Line: We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA).Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA.We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation.

View Article: PubMed Central - PubMed

Affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America. grants@chop.edu

ABSTRACT
Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence of a genome wide association (GWA) study of type 2 diabetes in adults. We examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at this locus with respect to our childhood obesity cohort, consisting of both Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study in our cohort of 418 Caucasian obese children (BMI>or=95th percentile), 2,270 Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA controls, we investigated the association of the previously reported variation at the FTO locus with the childhood form of this disease in both ethnicities. The minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for rs9939609 i.e. both r(2) = 1) in the Caucasian cases were 0.448 and 0.443 respectively while they were 0.391 and 0.386 in Caucasian controls respectively, yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08-1.47; P = 0.0022). Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and 0.115 respectively while they were 0.436 and 0.090 in AA controls respectively, yielding an OR of 1.05 (95% CI 0.91-1.21; P = 0.49) and of 1.31 (95% CI 1.050-1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the only SNP conferring significant risk in AA. We have therefore replicated and refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which captures the ancestral origin of the actual mutation. As such, variants in the FTO gene confer a similar magnitude of risk of obesity to children as to their adult counterparts and appear to have a global impact.

Show MeSH
Related in: MedlinePlus