Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP
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Date
2008-03
Authors
Grant, S.F.
Li, M.
Bradfield, J.P.
Kim, C.E.
Annaiah, K.
Santa, E.
Glessner, J.T.
Casalunovo, T.
Frackelton, E.C.
Otieno, George Ochieng
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
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$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 r2 = 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.
Description
doi:10.1371
Keywords
Citation
PLoS One. 2008 Mar 12;3(3):e1746. doi: 10.1371/