Causal effects of reproductive behaviors on the risk of osteoarthritis and rheumatoid arthritis：A Mendelian Randomization Study

Background: Reproductive behavior leads to drastic changes in hormones, which may affect the development of arthritis, but it is uncertain whether there is a causal relationship. This study used Mendelian randomization to examine whether there is a causal relationship between female reproductive practices and arthritis. Methods Summary statistical data for osteoarthritis and rheumatoid arthritis originated from two genome-wide association studies (GWAS). Public GWAS data with European ancestry were exploited to identify instrumental variables of age at first birth (AFB) and age at first sexual intercourse (AFS). Subsequently, Mendelian randomization analyses were mainly conducted with the inverse variance weighted (IVW) method. Furthermore, complementary sensitivity analyses were then conducted to assess the robustness of our results. Results Using the IVW method, we found evidence of causal relationships between hormonal reproductive behaviors and decreased rheumatoid arthritis (RA) risk (AFB and AFS, odds ratio (OR) [95% CI], 0.837[0.747–0.938], and 0.634[0.496–0.811], respectively). Both AFB and AFS seem to be negatively associated with knee osteoarthritis (OA) risk (AFB and AFS, OR [95% CI], 0.828[0.789–0.870], and 0.537[0.470–0.811], respectively). Only AFS was negatively associated with hip OA risk. (OR [95% CI], 0.788[0.682–0.911]). The findings of this study were verified by the results from sensitivity analysis. Conclusion This Mendelian randomization study suggests that both AFS and AFB seem to be negatively associated with arthritis risk.