Physical activity, genetic predisposition and the risk of rheumatoid arthritis: a prospective cohort study

Physical activities have consistently been associated with rheumatoid arthritis risk. However, there is limited evidence regarding their associations according to different genetic susceptibility to the disease, and it remains poorly understood whether systemic inflammation and lipids may mediate this association.

To investigate the association between physical activity and risk of rheumatoid arthritis, a multivariable Cox regression was performed using data from 351,857 participants in UK Biobank cohort. Additionally, we assessed the interaction of physical activity with polygenic risk score (PRS) for rheumatoid arthritis. We further estimated the percentage of total association between physical activity and rheumatoid arthritis that is mediated by C-reactive protein (CRP) and lipids.

A lower risk of rheumatoid arthritis was associated with the moderate and high level of physical activity (HR = 0.77, 95%CI = 0.70-0.84 and HR = 0.82, 95%CI = 0.75-0.89, respectively), and this association was stronger with five year after baseline. Separated by intensity of physical activity, only vigorous activity was associated with reduced risk of rheumatoid arthritis. A significant interaction was observed between physical activity and PRS for rheumatoid arthritis, indicating stronger association in those with low or medium genetic predisposition to rheumatoid arthritis. Furthermore, BMI and CRP was found to mediate 33.73% and 32.89% of the associations between physical activity and rheumatoid arthritis, while high-density lipoprotein (HDL) mediated 15.61% of the association.

We observed an inverse association between physical activity and risk of rheumatoid arthritis in UK biobank, which was stronger in those with low or medium PRS. BMI, CRP and HDL may be key intermediates in the association, suggesting them as potential monitoring biomarker for physical activity intervention to prevent rheumatoid arthritis.