Department of Endocrinology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510080, China.
J Clin Endocrinol Metab. 2023 Apr 13;108(5):1075-1083. doi: 10.1210/clinem/dgac683.
Both Graves disease (GD) and inflammatory bowel disease (IBD) are common autoimmune diseases that severely damage a patient's quality of life. Previous epidemiological studies have suggested associations between GD and IBD. However, whether a causal relationship exists between these 2 diseases remains unknown.
To infer a causal relationship between GD and IBD using bidirectional 2-sample Mendelian randomization (MR).
We performed bidirectional 2-sample MR to infer a causal relationship between GD and IBD using genome-wide association study summary data obtained from Biobank Japan and the International Inflammatory Bowel Disease Genetic Consortium. Several methods (random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO) were used to ensure the robustness of the causal effect. Heterogeneity was measured based on Cochran's Q value. Horizontal pleiotropy was evaluated by MR-Egger regression and leave-one-out analysis.
Genetically predicted IBD may increase the risk of GD by 24% (odds ratio [OR] 1.24, 95% CI 1.01-1.52, P = .041). Crohn disease (CD) may increase the risk of GD, whereas ulcerative colitis (UC) may prevent patients from developing GD. Conversely, genetically predicted GD may slightly increase the risk of CD, although evidence indicating that the presence of GD increased the risk of UC or IBD was lacking. Outlier-corrected results were consistent with raw causal estimates.
Our study revealed a potentially higher comorbidity rate for GD and CD. However, UC might represent a protective factor for GD. The underlying mechanism and potential common pathways await discovery.
格雷夫斯病（GD）和炎症性肠病（IBD）都是常见的自身免疫性疾病，严重损害患者的生活质量。先前的流行病学研究表明 GD 和 IBD 之间存在关联。然而，这两种疾病之间是否存在因果关系尚不清楚。
使用双向两样本 Mendelian 随机化（MR）推断 GD 和 IBD 之间的因果关系。
我们使用来自日本生物银行和国际炎症性肠病遗传联盟的全基因组关联研究汇总数据，进行双向两样本 MR 分析，以推断 GD 和 IBD 之间的因果关系。采用随机效应逆方差加权、加权中位数、MR-Egger 回归和 MR-PRESSO 等几种方法（MR-Egger 回归和单倍型缺失分析）来确保因果效应的稳健性。异质性基于 Cochran's Q 值进行测量。水平多效性通过 MR-Egger 回归和单倍型缺失分析进行评估。
遗传预测的 IBD 可能使 GD 的发病风险增加 24%（比值比 [OR] 1.24，95% CI 1.01-1.52，P =.041）。克罗恩病（CD）可能会增加 GD 的发病风险，而溃疡性结肠炎（UC）可能会阻止患者发生 GD。相反，遗传预测的 GD 可能会略微增加 CD 的发病风险，尽管缺乏 GD 存在会增加 UC 或 IBD 发病风险的证据。经过异常值校正的结果与原始因果估计一致。
我们的研究揭示了 GD 和 CD 之间潜在的更高的共病率。然而，UC 可能是 GD 的保护因素。其潜在的机制和潜在的共同途径有待发现。
