维生素D水平与系统性红斑狼疮患病风险的孟德尔随机化研究

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

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D 3水平[25(OH)D 3]、25-羟维生素D 3差向异构体水平[C3-epi-25(OH)D 3]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)D 3水平和C3-epi-25(OH)D 3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)D 3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)D 3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)D 3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)D 3。

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.