Ding Yang, Fan Shasha, Tang Yi, He Mengjiao, Ren Mingyang, Shi Yunjuan, Tao Xiaohua, Lu Wei
Health Management Center, Department of Dermatology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou 310014, China.
Departments of Environmental Health, School of Public Health, Hangzhou Normal University, Hangzhou 310009, China.
Metabolites. 2022 Dec 23;13(1):27. doi: 10.3390/metabo13010027.
We evaluated the causal effects of blood lipid levels on systemic lupus erythematosus with a two-sample Mendelian randomization analysis. Independent single-nucleotide polymorphisms related to blood lipids levels (p < 5 × 10−8) were selected as instrumental variables (IVs) from a published genome-wide association study (GWAS). SLE GWAS analysis that included 4036 cases and 6959 controls of European ancestry provided the related roles between instrumental variables and result (SLE). The causal effects were evaluated with two-sample Mendelian randomization (MR) analyses. According to the inverse-variance weighted approaches, genes predictive of increased LDL cholesterol (OR: 1.131; 95% CI: 0.838, 1.528; p = 0.420), HDL cholesterol (OR: 1.093; 95% CI: 0.884, 1.352; p = 0.412), triglycerides (OR: 0.903; 95% CI: 0.716, 1.137; p = 0.384), Apolipoprotein A-I (OR: 0.854; 95% CI: 0.680, 1.074; p = 0.177), and Apolipoprotein B (OR: 0.933; 95% CI: 0.719, 1.211; p = 0.605) were not causally related to the risk of SLE, consistent with multivariate Mendelian randomization analysis. The reverse-MR analyses showed no massive causal roles between SLE and LDL cholesterol (OR: 0.998; 95% CI: 0.994, 1.001; p = 0.166) as well as Apolipoprotein B (OR: 0.998; 95% CI: 0.994, 1.001; p = 0.229). Nevertheless, a causal role of SLE in decreasing HDL cholesterol (OR: 0.993; 95% CI: 0.988, 0.997; p = 0.002), triglycerides (OR: 0.996; 95% CI: 0.993, 0.999; p = 0.010), and Apolipoprotein A-I (OR: 0.995; 95% CI: 0.990, 0.999; p = 0.026) was validated to some extent. Our study found no causal association between abnormal blood lipids and SLE nor a causal effect between SLE and LDL cholesterol as well as Apolipoprotein B. Nevertheless, some evidence showed that SLE exerted a causal effect on lowering HDL cholesterol, Apolipoprotein A-I, and triglyceride levels.
我们通过两样本孟德尔随机化分析评估了血脂水平对系统性红斑狼疮的因果效应。从已发表的全基因组关联研究（GWAS）中选择与血脂水平相关的独立单核苷酸多态性（p < 5×10−8）作为工具变量（IVs）。纳入4036例病例和6959例欧洲血统对照的系统性红斑狼疮GWAS分析提供了工具变量与结果（系统性红斑狼疮）之间的相关关系。通过两样本孟德尔随机化（MR）分析评估因果效应。根据逆方差加权法，预测低密度脂蛋白胆固醇升高的基因（OR：1.131；95%CI：0.838，1.528；p = 0.420）、高密度脂蛋白胆固醇（OR：1.093；95%CI：0.884，1.352；p = 0.412）、甘油三酯（OR：0.903；95%CI：0.716，1.137；p = 0.384）、载脂蛋白A-I（OR：0.854；95%CI：0.680，1.074；p = 0.177）和载脂蛋白B（OR：0.933；95%CI：0.719，1.211；p = 0.605）与系统性红斑狼疮风险无因果关系，这与多变量孟德尔随机化分析一致。反向MR分析显示系统性红斑狼疮与低密度脂蛋白胆固醇（OR：0.998；95%CI：0.994，1.001；p = 0.166）以及载脂蛋白B（OR：0.998；95%CI：0.994，1.001；p = 0.229）之间无显著因果作用。然而，系统性红斑狼疮在降低高密度脂蛋白胆固醇（OR：0.993；95%CI：0.988，0.997；p = 0.002）、甘油三酯（OR：0.996；95%CI：0.993，0.999；p = 0.010）和载脂蛋白A-I（OR：0.995；95%CI：0.990，0.999；p = 0.026）方面的因果作用在一定程度上得到了验证。我们的研究发现血脂异常与系统性红斑狼疮之间无因果关联，系统性红斑狼疮与低密度脂蛋白胆固醇以及载脂蛋白B之间也无因果效应。然而，一些证据表明系统性红斑狼疮对降低高密度脂蛋白胆固醇、载脂蛋白A-I和甘油三酯水平有因果作用。
