Genome wide analysis reveals association of a FTO gene variant with epigenetic changes of several genes in human blood

FTO gene variants show the strongest association to obesity so far, but the role of the gene in obesity remains unclear. The FTO protein is a demethylation enzyme, which suggests that the link to obesity could be mediated through epigenetic changes. Herein, we determine the genome wide DNA methylation profile in blood from 47 female preadolescents and detect changes in five methylated regions, corresponding to six genes, associated with the FTO risk allele (rs9939609). In addition, we identify 20 differentially methylated regions associated with obesity. Our findings indicate that the effect of the FTO obesity risk allele may be mediated through epigenetic changes. Further, the identified regions might prove valuable biomarkers for the diagnosis and prognosis of obesity and comorbidites, such as cardiovascular disease. Bisulphite converted DNA from 47 girls were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2. Half of the subjects are carriers of the FTO obesity risk allele (AA) and half of the normal allele (TT). In addition, both obese and normal-weigh indiviudals were included.