Association of FTO variants with BMI, fat mass and waist in the isolated population of Sorbs in Germany

The association between common variants in the FTO gene with weight, adiposity, body mass index (BMI) and risk of obesity has now been widely-replicated in samples of European origin. Though the causal variant has yet to be identified, it most likely maps within a 47kb region of intron 1 of FTO. We evaluated the relationships between FTO variants and BMI and related traits in the Sorbic population, an isolate of Slavonic origin resident in Deutschland. In a sample of 929 Sorbs, we could replicate the previously-reported associations of intron 1 SNPs with BMI (e.g. p=8.5×10–5 for rs8050136). However, using genome-wide association data (Affymetrix 500k arrays) from 211 of these individuals, we also detected a second independent signal: a cluster of six highly-correlated SNPs mapping to intron 3 about 40–60 kb away from the originally reported SNPs (e.g. rs8053740: p=1.3×10–5 in the GWA, p=2×10–4 in the full set of 929 individuals). This second signal was substantiated by physiologically-consistent associations with waist circumference, fat mass, insulin and glucose levels. In conclusion, we extend the evidence that FTO-variants are associated with BMI by putatively identifying a second susceptibility-allele independent of that previously-described. Though further statistical analysis of this findings is hampered by the finite size of the Sorbic isolate, these findings should encourage other groups to seek alternative susceptibility variants within FTO (and other established susceptibility loci) using the opportunities afforded by analyses in populations with divergent mutational and/or demographic histories.