Objective The prevalence of adolescent idiopathic scoliosis (AIS) in China has been increasing year by year. However, the causal relationship between physical activity (PA) of varying intensities and AIS remains unclear. This study employs Mendelian randomization (MR) to investigate this potential causal effect.

Methods Based on summary data from genome-wide association studies (GWAS), univariable, multivariable, and two-step MR analyses for validation were performed. Causal estimates were primarily assessed using the inverse-variance weighted (IVW) method, supplemented by the weighted median method, MR-Egger regression, simple mode and weighted mode. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept test and leave-one-out analysis, were conducted to assess the robustness of the results.

Results 1) Univariable MR analysis revealed no significant causal relationship between AIS and overall physical activity or PA of different intensities. However, a causal association was observed between the duration of strenuous sports and a lower risk of AIS. 2) Multivariable MR results indicated that the causal effect of strenuous sports on the risk of AIS remained significant after adjusting for body mass index, osteoporosis and vitamin D levels, respectively. 3) The results of the mediation MR analysis show that highly correlated variables, such as adolescent BMI, did not demonstrate a mediating effect in the causal relationship between strenuous sports and risk of AIS.

Conclusions Higher duration of strenuous sports participation may be causally associated with a lower risk of AIS, providing suggestive MR-based genetic evidence that could inform future strategies for AIS prevention and correction.