Although we found no evidence of widespread non-additive genetic effects contributing to obesity and type 2 diabetes risk, we did find robust examples of recessive effects at the FTO and CDKAL1 loci.
In a case-control study with 829 participants, factors involved with metabolism and obesity were assessed, including biochemical lipid and liver markers, and the fat mass and obesity-associated (FTO) single nucleotide polymorphism (SNP) rs8050136.
More importantly, this study revealed that the association between having a risk allele of the FTO gene and BMI (and obesity status) is largely concentrated among individuals who were heavier at birth.
However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.
A strong observational association between obesity and DVT with or without PE, supported by a direct genetic association between the obesity-specific locus FTO and DVT with PE, implies that obesity is likely to be causally associated with DVT.
The FTO gene may influence pathways implicated in regulation of TL, which could help to explain some of the non-consistent relationship between weight phenotype and telomere length that is observed in population studies investigating obesity.
FTO gene variants have been associated with obesity phenotypes in sedentary and obese populations, but rarely with skeletal muscle and elite athlete phenotypes.
In conclusion, FTOrs9939609 was associated with obesity measures, especially in those with the MetS, which was further exacerbated by high dietary SFA intake at baseline and 7.5 y later.
A region of chromosome 16 containing the fat mass-and obesity-associated gene (FTO) is reproducibly associated with fat mass and body mass index (BMI), risk of obesity, and adiposity.
The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)).
Many of these loci were associated with only one trait domain, were consistent with results in African Americans, and overlapped with published findings, for instance central obesity and FTO.
Our aim was to identify whether the obesity-susceptible gene variants (rs9939609, rs9930506, and rs4783819 in fat mass and obesity-associated gene (FTO); rs12970134 and rs17782313 in melanocortin-4 receptor gene (MC4R); and rs7566605, rs13428113, and rs9308762 in insulin-induced gene 2 [INSIG2]) were associated with NAFLD.
Several independent genome-wide association studies recently identified two common polymorphisms, FTOrs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity.
Boys and pubertal adolescents are more prone to respond poorly to standard obesity care while those with greater baseline degree of obesity and carriers of the FTOobesity-predisposing allele are not.
Furthermore, FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic vulnerability in reward processing can increase predisposition to obesity.