Associations of FTO and CLOCK Genetic Variants with Emotional Eating and Reward-Related Appetite Regulation Among...

Background: Patterns of dysregulated eating, including overeating, frequent snacking, and heightened food cravings, are associated with an increased risk of obesity and metabolic disease. Eating behaviors are multidimensional and can influence many factors, including social, cultural, and biological processes. Emerging evidence suggests that genetic variation may contribute to inter-individual differences in appetite regulation and reward-related eating, potentially influencing susceptibility to dysregulated eating patterns and behaviors. Objectives: This exploratory, secondary analysis investigated possible relationships between the genetic variants FTO rs9939609, CLOCK rs1801260, MC4R rs17782313, and CD36 rs1761667 and eating behavior traits and postprandial appetite regulation in healthy young males. Methods: Thirty healthy males (27.7 ± 3.6 y; BMI 24.5 ± 2.7 kg/m²) completed the Three-Factor Eating Questionnaire (TFEQ-R18) and consumed a standardized burrito-style meal, with appetite tracked over four hours using visual analogue scales (VAS). VAS data were baseline-adjusted and summarized as incremental area under the curve (AUC) to generate two derived exploratory composites of appetite suppression and cravings suppression. Genotyping was performed using iPLEX MassARRAY, and associations were tested with ANOVA and linear regression models. Results: FTO rs9939609 was significantly associated with higher emotional eating scores (β = 11.67; 95% CI 3.50, 19.83; p = 0.007, unadjusted), and this association remained significant after false discovery rate (FDR) correction. CLOCK rs1801260 showed a nominal association with reduced postprandial cravings suppression (β = -59.17; 95% CI -104.98, -13.35; p = 0.013, unadjusted). No associations were observed for MC4R or CD36. Conclusions: This exploratory analysis found a strong association between FTO rs9939609 and emotional eating, as well as a nominal relationship between CLOCK rs1801260 and craving regulation. These findings should be interpreted as hypothesis-generating and require confirmation in larger cohorts.