Objectives: To determine whether age at menarche (AAM), age at first live birth (AFB), and estradiol levels are causally correlated with the development of systemic lupus erythematosus (SLE).
Methods: A two-sample Mendelian randomization (MR) analysis was performed after data was collected from a dataset of genome-wide association studies (GWASs) related to SLE (as outcome), and from open access databases to find statistics related to AAM, AFB, and estradiol levels (as exposure).
Result: In our study, a negative causal correlation between AAM and SLE was confirmed by MR analysis (MR egger: beta = 0.116, SE = 0.948, p = 0.909; weighted median: beta = -0.416, SE = 0.192, p = 0.030; and IVW: beta = -0.395, SE = 0.165, p = 0.016). However, there were no genetic causal effects of AFB and the estradiol levels on SLE, based on the results of MR analysis as follows: AFB (MR egger: beta = - 2.815, SE = 1.469, p = 0.065; Weighted median: beta = 0.334, SE = 0.378, p = 0.377; and IVW: beta = 0.188, SE = 0.282, p = 0.505) and the estradiol levels (MR egger: beta = 0.139, SE = 0.294, p = 0.651; weighted median: beta = 0.063, SE = 0.108, p = 0.559; IVW: beta = 0.126, SE = 0.097, p = 0.192).
Conclusions: Our findings revealed that AAM may be associated with increased risk of the development of SLE, while there were no such causal effects from AFB and estradiol levels.
Keywords: Mendelian randomization; age at first live birth; age at menarche; estradiol; systemic lupus erythematosus.