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Obesity, a major health concern, is influenced by an individual’s genetic makeup and lifestyle factors (eating, sedentary lifestyle, and sleep disruptions) that affect circadian clock and metabolism. This study investigates the impact of Clock gene variants rs6843722 and rs4864548 on obesity measures in the Pakistani population. Genetic-behavior interaction studies have focused on Western populations, overlooking South Asians. We included 306 overweight/obese and 306 normal-weight controls, matched for age and gender. Anthropometric measures (BMI, waist circumference, waist-to-height ratio, and body fat percentage) were taken using standard procedures while behavioral data (dietary and sleep-related behaviors, shiftwork, and physical activity) was collected by questionnaire. Genotyping was performed by Taqman assays. Data was analyzed using SPSS 19.0. Rank-based inverse normal transformation was executed for quantitative non-normal variables. The linear regression revealed that both Clock gene variants interacted significantly with dietary and sleep-related behaviors and low physical activity, impacting adiposity measures regardless of age and gender. Shiftwork interacted specifically with rs6843722, increasing body fat percentage. This study indicates that Clock gene variants, when interacting with lifestyle factors, play a substantial role in increasing obesity risk highlighting the link between lifestyle choices and disturbances in circadian rhythms controlled by Clock gene variations, ultimately leading to obesity. [ABSTRACT FROM AUTHOR]