Department of Rheumatology and Immunology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, 314000, Zhejiang, China.
The Yangtze River Delta Biological Medicine Research and Development Center of Zhejiang Province, Yangtze Delta Region Institution of Tsinghua University, Hangzhou, 314006, Zhejiang, China.
Metab Brain Dis. 2024 Aug;39(6):1109-1115. doi: 10.1007/s11011-024-01379-8. Epub 2024 Jul 17.
This study aims to investigate the causal relationship between primary Sjögren's syndrome (SS) and multiple sclerosis (MS) using a two-sample Mendelian randomization (MR) analysis to provide insights into their common mechanisms and implications for therapeutic strategies. We utilized data from Genome-Wide Association Studies (GWAS) for primary SS (1,290 cases and 213,145 controls) and MS (4,888 cases and 10,395 controls), restricted to European ancestry. Instrumental variables (IVs) were selected based on genetic variants associated with primary SS. The primary MR method was Inverse Variance Weighted (IVW), supplemented by MR Egger, Weighted Median, Simple Mode, and Weighted Mode algorithms to assess the bidirectional causal relationships between MS and primary SS. Sensitivity analyses, including MR-PRESSO and leave-one-out analysis, were conducted to ensure the robustness of our findings. After excluding SNPs with pleiotropic effects, 42 and 5 SNPs were identified as robust IVs for primary SS and MS, respectively. Our analysis revealed a significant protective effect of MS on primary SS, with IVW showing an OR of 0.896 (95% CI: 0.841-0.954, P = 0.001). No significant heterogeneity or horizontal pleiotropy was detected, supporting the reliability of the results. Our findings suggest a potential protective effect of MS against primary SS, indicating a negative causal association between these two autoimmune diseases. This adds valuable genetic evidence to the understanding of the complex interplay between primary SS and MS, offering new avenues for research and therapeutic interventions.
本研究旨在通过双样本孟德尔随机化（MR）分析探讨原发性干燥综合征（SS）和多发性硬化症（MS）之间的因果关系，以深入了解它们的共同机制及其对治疗策略的意义。我们利用原发性 SS（1290 例病例和 213145 例对照）和 MS（4888 例病例和 10395 例对照）的全基因组关联研究（GWAS）数据，这些数据仅限于欧洲血统。根据与原发性 SS 相关的遗传变异选择了工具变量（IVs）。主要的 MR 方法是逆方差加权（IVW），并补充了 MR Egger、加权中位数、简单模式和加权模式算法，以评估 MS 和原发性 SS 之间的双向因果关系。进行了敏感性分析，包括 MR-PRESSO 和遗漏分析，以确保我们的发现具有稳健性。在排除具有多效性效应的 SNP 后，分别确定了 42 个和 5 个 SNP 作为原发性 SS 和 MS 的稳健 IV。我们的分析表明 MS 对原发性 SS 具有显著的保护作用，IVW 显示 OR 为 0.896（95%CI：0.841-0.954，P=0.001）。未检测到显著的异质性或水平多效性，支持结果的可靠性。我们的研究结果表明 MS 对原发性 SS 具有潜在的保护作用，表明这两种自身免疫性疾病之间存在负向因果关系。这为理解原发性 SS 和 MS 之间的复杂相互作用提供了有价值的遗传证据，为研究和治疗干预提供了新的途径。
