The bigger picture of FTO—the first GWAS-identified obesity gene

Abstract

Single nucleotide polymorphisms (SNPs) that cluster in the first intron of fat mass and obesity associated (FTO) gene are associated obesity traits in genome-wide association studies. The minor allele increases BMI by 0.39 kg/m(2) (or 1,130 g in body weight) and risk of obesity by 1.20-fold. This association has been confirmed across age groups and populations of diverse ancestry; the largest effect is seen in young adulthood. The effect of FTO SNPs on obesity traits in populations of African and Asian ancestry is similar or somewhat smaller than in European ancestry populations. However, the BMI-increasing allele in FTO is substantially less prevalent in populations with non-European ancestry. FTO SNPs do not influence physical activity levels; yet, in physically active individuals, FTO's effect on obesity susceptibility is attenuated by approximately 30%. Evidence from epidemiological and functional studies suggests that FTO confers an increased risk of obesity by subtly changing food intake and preference. Moreover, emerging data suggest a role for FTO in nutrient sensing, regulation of mRNA translation and general growth. In this Review, we discuss the genetic epidemiology of FTO and discuss how its complex biology might link to the regulation of body weight.

N6‐methyladenosine modification in mRNA: machinery, function and implications for health and diseases

“…A and obesity FTO was the first gene to be experimentally shown to play a role in common obesity and energy metabolism in human. As mentioned above, an SNP in the first intron of FTO was shown to be associated with body mass index in multiple human populations and ethnic groups [68,107]. The increase in fat mass was found to be responsible for the increase in body mass index [108][109][110][111].…”

Body composition of parents and their infants : methodological, anthropometric, metabolic and genetic studies

“…Associations between the FTO genotype and BMI have been replicated in numerous studies (36,37) and such relationships between the FTO genotype and body fatness have also been presented (39). Although FTO is the locus with the strongest association with BMI, variation in FTO explains less than 1 % of the variation in BMI (36,37). Associations between the FTO genotype and body fatness, BMI and FM have also been found in children (38 …”

“…In this study the addition of each risk allele at the single nucleotide polymorphism, rs9939609, was associated with an increased risk for obesity (odds ratio=1.31) and an increased body weight of ≈ 1.0 kg. Associations between the FTO genotype and BMI have been replicated in numerous studies (36,37) and such relationships between the FTO genotype and body fatness have also been presented (39). Although FTO is the locus with the strongest association with BMI, variation in FTO explains less than 1 % of the variation in BMI (36,37).…”

“…Despite this fact, efforts to identity genetic loci associated with obesity have been unsuccessful until recently (36,37). However, with the introduction of large genome-wide association studies (GWAS) a number of obesity associated loci have been identified.…”

Syndrome de Bardet-Biedl : cils et obésité

“…À cet égard, l'étude des BBS, qui a permis de révéler un rôle direct du tissu adipeux, complémentaire de celui de l'axe hypothalamique, est sans doute emblématique des futures recherches à mettre en oeuvre pour l'exploration de voies potentiellement associées au développement de l'obésité, et aussi pour l'identification de nouveaux biomarqueurs. L'obésité, maladie complexe et multifactorielle, a déjà été abordée via de nombreuses approches haut débit allant des études d'associations de type GWAS (genome wide association study) [52], des recherches de variants structuraux de type CNV (copy number variation) [53] ou des études de variations épigénétiques [54], jusqu'aux analyses basées sur des transcriptomes [55], protéomes [56], métabolomes [57] et récemment, des liposomes [58] ou des sécrétomes [59]. Cependant, au vu de nos résultats sur la biologie du tissu adipeux, ou des récents travaux sur la communication pancréas-tissu adipeux [60], seule une approche multi-niveaux, intégrant les différentes techniques haut débit pourra déchiffrer la variété des signaux et des communications interorganes (cross-talks) intervenant dans l'obésité ( Figure 1C).…”