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• Healthy sleep score demonstrated inverse associations with MD. • Healthy sleep pattern was associated with a reduced risk of MD when compared to those with poor sleep pattern at each group of physical activity, coffee intake, tea intake and genetic risk. • Encouraging healthy sleep pattern might be a great contributor to reducing the global burden of MD. Sleep behaviors were believed to be associated with mental disorders (MD). However, the underlying mechanism of such association relationship, especially the role of multiple lifestyle factors in it remains unclear. A total of 402,290 participants from UK Biobank who don't have MD at baseline were included. They were divided into poor, intermediate and healthy sleep patterns according to the sleep score, which was calculated based on the data collecting from five sleep behaviors. Cox proportional hazard model was used to estimate the associations between sleep behaviors and MD. The associations were further estimated when taking lifestyle factors such as physical activity, coffee intake, tea intake and genetic susceptibility into account. Healthy sleep pattern was associated with lower risk of overall MD status (HR,0.41, 95%CI,0.39–0.43), depressive disorders (HR,0.34, 95%CI,0.31–0.37) and anxiety disorders (HR,0.46, 95%CI,0.41–0.79), compared with poor sleep pattern. And in each subgroup of physical activity, tea intake, coffee intake, age and genetic risk scores (GRS), healthy sleep pattern could partly offset the risk of diseases. Our study suggested healthy sleep behaviors could diminish the negative effect from genetic predisposition and lifestyle factors on the risk of MD, highlighting the benefit of healthy sleep pattern. [ABSTRACT FROM AUTHOR]