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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). 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). 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). 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.


Yongbin Zhang, Yuxuan Fang, Nan Xu, Longlong Tian, Xingxing Min, Guiyu Chen, Tiantian Dai, Nianxing Liu, Xuanhan Wang, Yujun Rao, Guoqing Li. The causal effects of age at menarche, age at first live birth, and estradiol levels on systemic lupus erythematosus: A two-sample Mendelian randomization analysis. Lupus. 2023 Jul;32(8):928-935

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PMID: 37246529

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