Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Department of Pediatric Allergy, Immunology & Rheumatology, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong, China.
Front Immunol. 2024 Jan 29;15:1273358. doi: 10.3389/fimmu.2024.1273358. eCollection 2024.
Previous observational studies have established a correlation between Graves' disease(GD) and systemic lupus erythematosus(SLE). However, whether a causal relationship exists between these two diseases remains unknown.We utilized Mendelian randomization to infer the causal association between GD and SLE.
This study employed GWAS summary statistics of GD and SLE in individuals of Asian descent. The random effect inverse variance weighted (IVW) method was utilized to aggregate the causal effect estimates of all SNPs. Cochran's Q values were computed to evaluate the heterogeneity among instrumental variables. Sensitivity analyses such as MR-Egger method, median weighting method, leave-one-out method, and MR-PRESSO method were used to test whether there was horizontal pleiotropy of instrumental variables.
Our study found genetically predicted GD may increase risk of SLE (OR=1.17, 95% CI 0.99-1.40, p=0.069). Additionally, genetically predicted SLE elevated the risk of developing GD by 15% (OR=1.15, 95% CI 1.05-1.27, p= 0.004). After correcting for possible horizontal pleiotropy by excluding outlier SNPs, the results suggested that GD increased the risk of SLE (OR=1.27, 95% CI 1.09-1.48, =0.018), while SLE also increased the risk of developing GD (OR=1.13, 95% CI 1.05-1.22, =0.003).
The findings of the study indicate that there may be a correlation between GD and SLE, with each potentially increasing the risk of the other. These results have important implications for the screening and treatment of patients with co-morbidities in clinical settings, as well as for further research into the molecular mechanisms underlying the relationship between GD and SLE.
先前的观察性研究已经确立了格雷夫斯病（GD）与系统性红斑狼疮（SLE）之间的相关性。然而，这两种疾病之间是否存在因果关系尚不清楚。我们利用孟德尔随机化来推断 GD 和 SLE 之间的因果关联。
本研究利用亚洲人群 GD 和 SLE 的 GWAS 汇总统计数据。采用随机效应逆方差加权（IVW）方法对所有 SNP 的因果效应估计值进行聚合。计算 Cochran's Q 值以评估工具变量之间的异质性。采用 MR-Egger 方法、中位数加权法、逐一剔除法和 MR-PRESSO 法等敏感性分析方法，检测工具变量是否存在水平多效性。
我们的研究发现，遗传预测的 GD 可能会增加 SLE 的发病风险（OR=1.17，95%CI 0.99-1.40，p=0.069）。此外，遗传预测的 SLE 使 GD 的发病风险增加了 15%（OR=1.15，95%CI 1.05-1.27，p=0.004）。在排除异常 SNP 后，对可能存在的水平多效性进行校正，结果表明 GD 增加了 SLE 的发病风险（OR=1.27，95%CI 1.09-1.48， =0.018），而 SLE 也增加了 GD 的发病风险（OR=1.13，95%CI 1.05-1.22， =0.003）。
本研究的结果表明，GD 和 SLE 之间可能存在相关性，两者相互作用可能会增加彼此的发病风险。这些结果对临床实践中合并症患者的筛查和治疗具有重要意义，也为进一步研究 GD 和 SLE 之间的关系的分子机制提供了依据。
