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OBJECTIVE: We examined whether meal timing is associated with long-term weight-loss maintenance and whether meal timing interacts with a genome-wide polygenic score (PRS-BMI) on body weight-related outcomes. We then examined the interaction of meal timing with 97 BMI-related single-nucleotide polymorphisms on obesity outcome.METHODS: Participants (N = 1195, mean age 41.07 [SD 12.68] years, female 80.8%, baseline mean BMI 31.32 [SD 5.53] kg/m) were adults with overweight or obesity from the Obesity, Nutrigenetics, Timing, and Mediterranean (ONTIME) study. We developed a PRS-BMI to assess the genetic risk for obesity and estimated the timing of the midpoint of meal intake. We also calculated the success in long-term weight-loss maintenance after a dietary obesity treatment (at least 3 years). Linear regression analyses were performed for association and interaction assessments.RESULTS: Each hour of delay in meal timing was associated with 2.2% higher long-term body weight (β [SE] = 2.177% [1.067%]; p = 0.042) (i.e., with lower weight-loss maintenance following dietary obesity treatment). There was a significant interaction between meal timing and PRS-BMI (p = 0.008); BMI increased by more than 2 kg/m for every hour of delay in meal timing in individuals with high PRS-BMI (β [SE] = 2.208 [0.502] kg/m; p = 1.0E-5), whereas no associations were evident for those with lower genetic risk.CONCLUSIONS: Meal timing is associated with weight-loss maintenance and may influence the association between obesity genetics and BMI. Findings underscore the importance of personalized obesity management.