FTO genotype and weight status among children: assessing mediating and independent effects of child eating behaviors
Authors: Emond Jennifer A , Tovar Alison , Lansigan Reina , Li Zhigang , Gilbert‐Diamond Diane 
Published: November 2023

Variations in the Fat Mass and Obesity Associated (FTO) gene single nucleotide polymorphism rs9939609 are related to an increased risk of obesity among adults and children, although the mechanisms are unclear. FTO rs9939609 polymorphisms have also been associated with loss of control over eating and decreased satiety responsiveness among children, suggestive of a possible behavioral mechanism. We therefore explored if child eating behaviors mediated the relation between FTO genotype and overweight/obese status among 178 unrelated 9–10 year olds. During a study visit, child's height and weight were measured and a buccal sample for FTO rs9939609 polymorphism genotyping was provided. A parent or guardian completed the Child Eating Behavior Questionnaire to assess eight domains of child eating behaviors. A causal steps approach using a series of adjusted logistic regression models was used to assess the mediating effect of each child eating behavior on the relation between FTO genotype and overweight/obese status (>=85th age‐ and sex‐adjusted BMI percentile); all models were adjusted for child gender, maternal education and household income. Sobel's z‐test was also computed to assess the statistical significance of each mediating effect. The distribution of FTO rs9939609 genotype in our sample was similar to population estimates: TT=34.8%, AT=48.9%, AA=16.3%. Overall, 23.0% of children were overweight/obese; rates were highest for those with the AA FTO genotype (41.4%; p=0.04) yet were equivalent among children with the TT or AA genotypes (19.5%; p=0.81). In adjusted logistic regression models that did not include FTO genotype, greater food responsiveness (aOR: 3.01; p<0.01) and emotional overeating (aOR: 3.68; p<0.01) were each independently associated with overweight/obesity. Results from the causal steps approach suggested that increased food responsiveness partially mediated the positive relation between AA FTO genotype and weight status. Specifically, the adjusted odds of overweight/obesity related to the AA (vs. TT) FTO genotype decreased by 19.7% from 4.88 (p=0.007) to 3.92 (p=0.028) once further adjusted for food responsiveness, and food responsiveness remained statistically associated with the odds of being overweight/obese in that model (aOR: 2.92; p<0.01). The Sobel's z‐test demonstrated that indirect effect was of borderline significance (p=0.12). In comparison, increased emotional over‐eating was statistically associated with overweight/obesity in an adjusted logistic regression model, independent of AA FTO genotype, with no evidence of a mediating effect (Sobel's z‐test p‐value=0.33). In summary, increased food responsiveness may be a possible behavioral mechanism whereby variations in the FTO rs9939609 polymorphism lead to excess weight gain among children, while emotional overeating may act independently of FTO genotype on influencing excess weight gain.Support or Funding InformationThis research was support by the NIH (HD076097).