Causal Relationships Between Total Physical Activity and Ankylosing Spondylitis: A Mendelian Randomization Study

Area of Science:

• Genetics
• Epidemiology
• Rheumatology

Background:

• Limited research exists on the association between physical activity (PA) and ankylosing spondylitis (AS) risk.
• Understanding the causal link between PA and AS is crucial for developing effective prevention strategies.

Purpose of the Study:

• To investigate the causal relationship between various measures of physical activity and the risk of developing ankylosing spondylitis (AS).
• To differentiate the impact of total physical activity versus physical activity intensity on AS risk.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) approach using genome-wide association studies (GWAS) summary statistics.
• Utilized the inverse variance weighted (IVW) method as the primary analysis, supplemented by sensitivity, pleiotropy, and heterogeneity analyses to ensure result robustness.

Main Results:

• Accelerometer-based total physical activity demonstrated a statistically significant protective association with AS risk (OR = 0.9995, P = 0.014).
• No significant causal relationship was found between accelerometer-measured high-intensity PA (acceleration fraction >425 mg) and AS.
• Self-reported measures of vigorous PA and moderate-to-vigorous PA also showed no significant causal association with AS risk.

Conclusions:

• Total physical activity (TPA) exerts a protective effect on the risk of ankylosing spondylitis (AS).
• Physical activity intensity, whether vigorous or moderate-to-vigorous, is not causally associated with AS.
• Recommendations for AS prevention should focus on increasing overall TPA rather than solely on enhancing PA intensity.