[Associations between vitamin D levels and systemic lupus erythematosus risk:a Mendelian randomized study].

Objective: To explore the causal effects of the serum Vitamin D levels on the risk of systemic lupus erythematosus (SLE). Methods: A two-sample Mendelian randomization (MR) study was performed to infer the causality. Three Genome-wide association studies (GWAS) for circulating Vitamin D levels, including 25-hydroxyvitamin D [25(OH)D], 25-hydroxyvitamin D3 [25(OH)D3] and C3-epimer of 25-hydroxyvitamin D3 [C3-epi-25(OH)D3] published in 2020, and one GWAS for SLE published in 2015 were utilized to analyze the causal effects of the serum Vitamin D levels on the risk of SLE. MR analyses were conducted using the inverse-variance weighted method (IVW), weighted median, MR-Egger methods, MR-pleiotropy residual sum and outlier (MR-PRESSO) method. Results: 34, 29 and 6 SNPs were respectively selected as instrumental variables to analyze the causal association of total 25 (OH) D level, 25 (OH) D3 level and C3-epi-25 (OH) D3 level with the risk of SLE. The MR results showed that each standard deviation decrease in the level of 25(OH)D3 would result in 14.2% higher risk of SLE (OR, 0.858; 95%CI, 0.753-0.978; P=0.022). The levels of 25(OH)D and C3-epi-25(OH)D3 had null associations with risk of SLE (OR, 0.849; 95%CI, 0.653-1.104; P=0.222; OR, 0.904; 95%CI, 0.695-1.176; P=0.452). Conclusion: This study have identified a causal effect of 25(OH)D3 on increased risk of SLE. These findings highlighted the significance of active monitoring and prevention of SLE in population of low Vitamin D levels.目的： 探讨维生素D水平与系统性红斑狼疮（SLE）患病风险之间的因果关系。 方法： 采用双样本孟德尔随机化（MR）研究方法，利用2020年发表的总25-羟维生素D水平［25（OH）D］、25-羟维生素D3水平［25（OH）D3］、25-羟维生素D3差向异构体水平［C3-epi-25（OH）D3］等循环维生素D水平相关的3个全基因组关联分析（GWAS）数据集和2015年发表的1个SLE GWAS数据集，通过逆方差加权法（IVW）、加权中位数法（WME）、MR-Egger法、MR多效残差和离群值法（MR-PRESSO）分析维生素D水平对SLE患病风险的因果效应。 结果： 分析总25（OH）D水平、25（OH）D3水平和C3-epi-25（OH）D3水平与SLE患病风险因果关联的有效工具变量分别为34、29和6个SNP位点。MR分析结果显示，25（OH）D3水平每降低一个标准差，SLE风险增加14.2%（OR，0.858；95%CI，0.753~0.978；P=0.022），而总25（OH）D水平和C3-epi-25（OH）D3水平与SLE风险的因果关联不具有统计学意义（OR，0.849；95%CI，0.653~1.104；P=0.222；OR，0.904；95%CI，0.695~1.176；P=0.452）。 结论： 25（OH）D3与SLE患病风险存在因果关联，提示低维生素D人群应积极监测并注意预防SLE发生，SLE患者应适当补充25（OH）D3。.