Ma Lan, Jiang Xue, Hou Zhijia, Li Dongmei
Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Capital Medical University, Beijing, China.
Adv Ophthalmol Pract Res. 2024 Nov 22;5(1):66-72. doi: 10.1016/j.aopr.2024.11.004. eCollection 2025 Feb-Mar.
This Mendelian randomization (MR) analysis study aimed to investigate the genetic causal relationship between non-thyroidal autoimmune diseases (ADs) and Graves' ophthalmopathy (GO).
Single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis vulgaris (PV), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) were obtained from the IEU Open genome-wide association studies (GWAS) database, GWAS data for GO were obtained from the FinnGen database. Bidirectional MR analysis was conducted using inverse variance weighted (IVW) method, weighted median (WM) method and MR-Egger test. Cochran's Q statistic was used to assess the heterogeneity between SNP estimates. MR-Egger regression was used to evaluate horizontal pleiotropy and MR pleiotropy residual sum and outlier (MR-PRESSO) test was used to detect the outliers.
For non-thyroidal ADs, the forward MR results using the IVM method showed that T1D (OR = 1.259, 95%CI 1.026-1.5465; = 0.028) and SLE (OR = 1.807, 95%CI 1.229-2.655; = 0.003) were correlated with the risk of GO at the genetic level, while there was no evidence showing that IBD, MS, PV and RA were correlated with GO. In the reverse MR study, there was a significant increase in the risk of developing T1D in GO (OR = 1.135, 95%CI 1.018-1.265; = 0.022), but pleiotropy and heterogeneity existed.
In the European population, there is strong genetic evidence that patients with T1D and SLE have a higher risk of developing GO, whereas the effect of GO on ADs is unclear.
本孟德尔随机化（MR）分析研究旨在探讨非甲状腺自身免疫性疾病（ADs）与格雷夫斯眼病（GO）之间的遗传因果关系。
从IEU开放全基因组关联研究（GWAS）数据库中获取与炎症性肠病（IBD）、多发性硬化症（MS）、寻常型银屑病（PV）、1型糖尿病（T1D）、系统性红斑狼疮（SLE）和类风湿性关节炎（RA）相关的单核苷酸多态性（SNP），GO的GWAS数据来自芬兰基因数据库。使用逆方差加权（IVW）法、加权中位数（WM）法和MR-Egger检验进行双向MR分析。采用 Cochr an's Q统计量评估SNP估计值之间的异质性。使用MR-Egger回归评估水平多效性，并使用MR多效性残差和异常值（MR-PRESSO）检验检测异常值。
对于非甲状腺ADs，使用IVM方法的正向MR结果显示，T1D（OR = 1.259，95%CI 1.026 - 1.5465；P = 0.028）和SLE（OR = 1.807，95%CI 1.229 - 2.655；P = 0.003）在基因水平上与GO风险相关，而没有证据表明IBD、MS、PV和RA与GO相关。在反向MR研究中，GO患者发生T1D的风险显著增加（OR = 1.135，95%CI 1.018 - 1.265；P = 0.022），但存在多效性和异质性。
在欧洲人群中，有强有力的遗传证据表明T1D和SLE患者发生GO的风险较高，而GO对ADs的影响尚不清楚。
