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OBJECTIVE: In this cross-sectional study, we aim to investigate the interactions between obesity, siesta behavior, and the genetic propensity for siesta in a Mediterranean population, in whom siesta is deeply rooted.METHODS: We applied a previously generated Siesta-Polygenic Score (PGS) in the ONTIME study (n = 1278). Siesta and other Mediterranean lifestyle behaviors were characterized using questionnaires. We further determined obesity grade. Secondarily, we measured weight loss during treatment as well as long-term weight-loss maintenance. Logistic regression analyses were performed to address our aim.RESULTS: A total of 42.4% of the population usually took siesta. A significant genetic influence on siesta propensity was found, with a higher genetic predisposition linked to taking siesta more frequently (odds ratio [OR] = 1.17, 95% CI: 1.03-1.32; p = 0.015). Participants with a higher genetic propensity for siesta showed poorer dietary habits (p < 0.05). Among individuals with a high genetic propensity for siesta, we found that those who usually take siesta have lower odds of having obesity (p = 0.038) compared with those who do not. Similarly, in exploratory analysis, among individuals with a high genetic propensity for siesta, we found that those who usually take siesta have higher odds of weight-loss success (p = 0.007) compared with those who do not.    CONCLUSIONS: Considering the ongoing debate regarding whether siesta is beneficial or detrimental, our findings suggest that individual genetic predisposition to siesta might influence the association between siesta and health.