The role of eating behavior traits in mediating genetic susceptibility to obesity

Background Genome-wide association studies (GWASs) have identified several genes associated with obesity. The mechanisms through which these genes affect body weight are not fully characterized. Recent studies suggest that eating behavior (EB) traits could be involved, but only a few EB traits were investigated. Objective This study aimed to investigate whether genetic susceptibility to obesity is mediated by EB traits (cognitive restraint, disinhibition, hunger) and their subscales. We hypothesized that EB traits, and their subscales, partly mediate this association. Design Adult individuals (n = 768) who participated in the Quebec Family Study were included in this cross-sectional study. A genetic risk score (GRS) of obesity was calculated based on the 97 genetic variants recently identified in a GWAS meta-analysis of body mass index (BMI). EB traits and their subscales were assessed with the use of the Three-Factor Eating Questionnaire. Regression analyses with age and sex as covariates were used to investigate the associations between GRS, EB traits, BMI, and WC and whether the association between GRS and obesity is mediated by EB traits, which represents the indirect effect of GRS on obesity. Results The GRS of obesity was positively associated with BMI (β = 0.19 ± 0.04, P < 0.0001) and WC (β = 0.46 ± 0.10, P < 0.0001). Regression analyses also revealed that the association between GRS of obesity and BMI was partly mediated by disinhibition and susceptibility to hunger (βindirect = 0.09 ± 0.03, P = 0.0007, and βindirect = 0.04 ± 0.02, P = 0.02, respectively). Habitual and situational susceptibility to disinhibition (βindirect = 0.08 ± 0.03, P = 0.002 and βindirect = 0.05 ± 0.02, P = 0.003, respectively) as well as internal and external locus of hunger (βindirect = 0.03 ± 0.02, P = 0.03 for both) were also found to mediate the association between GRS of obesity and BMI. The same trends were observed with WC. Conclusions The results of this study indicate that the genetic susceptibility to obesity is partly mediated through undesirable EB traits, which suggests that they could be targeted in obesity treatment and prevention. This trial was registered at clinicaltrials.gov as NCT03355729.