There is a lack of prospective cohort studies exploring the associations between the timing of physical activity and incident depression. This study aimed to explore the associations and to investigate whether genetic predisposition of depression may modify the associations. The study using data from UK Biobank, included 76,218 participants. The data of total physical activity (TPA) and moderate-to-vigorous physical activity (MVPA) were collected by accelerometer measurements over 7 consecutive days. Cox proportional hazard models were performed to calculate the hazard ratio (HR) and 95 % confidence interval (CI). In total, compared to the midday-afternoon group, participants in the early morning group of TPA had a lower risk of depression (HR: 0.76, 95 % CI: 0.65-0.89). Compared to the inactive group, a lower risk of incident depression was found among the participants with MVPA in the morning (HR: 0.80, 95 % CI: 0.67-0.96) and middy-afternoon (HR: 0.82, 95 % CI: 0.70-0.96). The joint effect analysis of the timing of TPA and genetic predisposition for incident depression showed that compared to the participants with a high genetic predisposition and in the middy-afternoon group of TPA, early morning group had a reduced risk of depression regardless of genetic predisposition. However, in subgroup analyses for genetic predisposition, only participants with a high genetic predisposition to depression benefited from TPA in the early morning. TPA in the early morning and MVPA in the morning and middy-afternoon were significantly associated with a lower depression risk, especially for participants with a higher genetic predisposition of depression.
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