Replacing Sedentary Time with Physical Activity to Reduce Type 2 Diabetes Risk: Insights from Genetic Causal Evidence
Yuan Xinzhu, Zhang Shijie, Sima Chuxin
Background: Sedentary behavior and physical activity are known lifestyle factors associated with type
2 diabetes (T2D), yet their causal roles remain uncertain.
Methods: We performed a bidirectional two-sample Mendelian randomization (MR) analysis to
investigate the causal effects of three leisure sedentary behaviors (television watching, computer use,
driving) and two physical activity phenotypes (moderate-to-vigorous [MVPA] and vigorous physical
activity [VPA]) on T2D. GWAS summary statistics were derived from large-scale European cohorts. The
inverse variance weighted (IVW) method was used as the primary analytical approach, complemented
by weighted median and MR-Egger methods. Sensitivity analyses assessed heterogeneity and horizontal
pleiotropy.
Results: Forward MR analysis showed a significant positive causal effect of television watching on T2D
(IVW OR = 1.760, P < 0.001). VPA demonstrated an inverse association trend (IVW OR = 0.535, P =
0.080), although this did not reach the conventional threshold for statistical significance (P < 0.05). No
significant associations were found for computer use, driving, or MVPA. Reverse MR analyses indicated
no significant causal effect of T2D on any behavioral traits. Sensitivity analyses did not detect notable
pleiotropy.
Conclusion: Our findings provide genetic evidence supporting a causal role of specific sedentary
behaviors and physical activity in T2D development. Interventions targeting television viewing may
offer potential benefits for primary prevention.
