The Common FTO rs9939609 Polymorphism Interacts with Sleeping and Eating Windows to Affect Predisposition to Type 2 Diabetes

<b>Background:</b> The common fat mass and obesity-associated (<i>FTO</i>) gene variant rs9939609 has been linked to elevated risk of obesity and Type 2 diabetes mellitus (T2DM). Eating and sleeping windows gained clinical interest as factors in weight maintenance and have been linked to T2DM risk. <b>Objective:</b> To study the association and interaction between the common <i>FTO</i> rs9939609 variant and eating and sleeping windows to affect T2DM risk in a large community cohort. <b>Methods:</b> This cross-sectional study included 12,254 adult participants. Genetic, anthropometric, and lifestyle behaviors data including eating and fasting windows were analyzed. Logistic and linear regression models, as well as chi-square tests, were applied under additive, dominant, and recessive genetic models (adjusted for age, sex, and BMI). <b>Results:</b> Significant associations between <i>FTO</i> rs9939609 x eating and sleeping window interactions were demonstrated in relation to T2DM risk. Longer eating windows and later last meal timing were associated with an increased risk for T2DM under the additive model (OR = 1.029, 95% CI = 1.002-1.055, and OR = 1.066, 95% CI = 1.012-1.122, respectively), while longer fasting windows were found to be protective under additive model (OR = 0.972, 95% CI = 0.947-0.998). Later bedtime onset was associated with an increased risk for T2DM under additive model (OR = 1.101, 95% CI = 1.005-1.220). Hours of night sleep significantly interacted with <i>FTO</i> rs9939609 under additive genetic model. <i>FTO</i> rs9939609 risk allele carriers with prolonged sleeping windows (OR = 1.137, 95% CI = 1.039-1.354) and poorer sleeping quality (OR = 1.185, 95% CI = 1.038-1.354) had increased risk of T2DM. <b>Conclusions:</b> Eating and fasting windows, late last meal timing, hours of night sleep, late bedtime onset, and poorer sleep quality are significantly associated with T2DM risk among <i>FTO</i> rs9939609 risk carriers and may reflect metabolic vulnerability associated with <i>FTO</i> risk alleles. These findings highlight potential behavioral modification to attenuate genetic risk and provide evidence for actionable prevention strategies in genetically predisposed populations.