This study investigates the causal relationships between sedentary behavior (SB), physical activity (PA), and sleep duration (SD) and obesity risk using Mendelian randomization (MR). The research analyzed genetic variants associated with SB, PA, and SD from genome-wide association studies (GWAS) and used these as instrumental variables (IVs) to assess their causal impact on obesity. The study found that four specific SBs—leisure screen time (LST), television watching, computer use, and driving—are causally linked to increased obesity risk. These associations were supported by eQTL analysis, which identified genetic variants associated with these SBs in both subcutaneous and visceral adipose tissues. The study also found no causal relationships between SB at work, sedentary commuting, PA, and SD with obesity. Enrichment analysis revealed that these genes are involved in biological pathways such as cortisol synthesis, thyroid hormone synthesis, and insulin secretion. The findings suggest that reducing specific SBs could be an effective strategy for obesity prevention. The study highlights the importance of genetic research in understanding the complex interplay between lifestyle behaviors and obesity. The results provide valuable insights into potential interventions to address obesity effectively. The study also emphasizes the need for further research and public health initiatives focused on reducing specific SBs.This study investigates the causal relationships between sedentary behavior (SB), physical activity (PA), and sleep duration (SD) and obesity risk using Mendelian randomization (MR). The research analyzed genetic variants associated with SB, PA, and SD from genome-wide association studies (GWAS) and used these as instrumental variables (IVs) to assess their causal impact on obesity. The study found that four specific SBs—leisure screen time (LST), television watching, computer use, and driving—are causally linked to increased obesity risk. These associations were supported by eQTL analysis, which identified genetic variants associated with these SBs in both subcutaneous and visceral adipose tissues. The study also found no causal relationships between SB at work, sedentary commuting, PA, and SD with obesity. Enrichment analysis revealed that these genes are involved in biological pathways such as cortisol synthesis, thyroid hormone synthesis, and insulin secretion. The findings suggest that reducing specific SBs could be an effective strategy for obesity prevention. The study highlights the importance of genetic research in understanding the complex interplay between lifestyle behaviors and obesity. The results provide valuable insights into potential interventions to address obesity effectively. The study also emphasizes the need for further research and public health initiatives focused on reducing specific SBs.