Genetic Predisposition, Sedentary Behavior and Incident Coronary Artery Disease: A Prospective Chinese Cohort Study.

Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST), and further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups. This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models. During a median follow-up of 11.60 years, 1156 CAD events were documented.Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95%CI: 0.27-1.28). Compared with participants with low genetic risk and low ST (<6 h/day), those with high genetic risk and high ST (≥10 h/day) had the highest CAD risk, with the hazard ratio (HR) and 95% confidence interval (95%CI) of 4.22 (2.65-6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with the HR (95%CI) of 1.21 (0.61-2.40), 1.57 (1.14-2.16), and 2.15 (1.40-3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST (Ptrend = 0.024). Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk.

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Conflict of Interest and Funding Source: The authors gratefully acknowledge all the staff and participants of the China-PAR project for their participation and contribution. This work was supported by Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2021-I2M-1-010, 2019-I2M-2-003, and 2017-I2M-1-004), the National Key Research and Development Program of China (2017YFC0211700, 2018YFE0115300), National Natural Science Foundation of China (82030102, 12126602, and 91857118). The sources of funding had no role in study design, data collection, analyses, interpretation, and decision to submit the article for publication. The authors declare that the results of the present study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the study do not constitute endorsement by the American College of Sports Medicine. None of the authors have a conflict of interest in relation to this manuscript.