Su Tao, Gan Ying, Ma Shulin, Wu Hongzhen, Lu Shilin, Zhi Min, Wang Bao, Lu Yi, Yao Jiayin
Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
Department of Anesthesiology, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
Diabetes Metab Syndr. 2024 May;18(5):103023. doi: 10.1016/j.dsx.2024.103023. Epub 2024 Apr 30.
Epidemiological studies have consistently demonstrated a high prevalence of concurrent autoimmune diseases in individuals with Graves' disease (GD).
The objective of this study is to establish a causal association between GD and autoimmune diseases.
We employed a two-sample Mendelian randomization (MR) to infer a causal association between GD and five autoimmune diseases, namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS), in the East Asian and European population. Genetic correlations were explored through linkage disequilibrium score regression analysis (LDSC). Finally, colocalization analyses were performed to investigate possible genetic foundations.
Bidirectional MR analysis indicated that genetically predicted GD increased the risk of RA (Odds Ratio (OR): 1.34, 95 % Confidence Interval (CI): 1.21 to 1.47, P < 0.001) and SLE (OR: 1.21, 95%CI: 1.08 to 1.35, P < 0.001) in the East Asian population. In contrast, we found that genetically predicted RA (OR: 1.14, 95%CI: 1.05 to 1.24, P = 0.002) and SLE (OR: 1.10, 95%CI: 1.03 to 1.17, P = 0.003) were associated with a higher risk of GD. The results have been partially validated in European cohorts. Colocalization analysis suggested the potential existence of shared causal variants between GD and other autoimmune diseases. In particular, gene ARID5B may play an important role in the incidence of autoimmune diseases.
This study has confirmed that GD was associated with RA and SLE and found a possible key gene ARID5B. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.
流行病学研究一直表明，格雷夫斯病（GD）患者中并发自身免疫性疾病的患病率很高。
本研究的目的是确定GD与自身免疫性疾病之间的因果关系。
我们采用两样本孟德尔随机化（MR）方法，推断东亚和欧洲人群中GD与五种自身免疫性疾病之间的因果关系，这五种疾病分别是类风湿性关节炎（RA）、系统性红斑狼疮（SLE）、克罗恩病（CD）、溃疡性结肠炎（UC）和肌萎缩侧索硬化症（ALS）。通过连锁不平衡评分回归分析（LDSC）探索遗传相关性。最后，进行共定位分析以研究可能的遗传基础。
双向MR分析表明，在东亚人群中，基因预测的GD会增加患RA（优势比（OR）：1.34，95%置信区间（CI）：1.21至1.47，P<0.001）和SLE（OR：1.21，95%CI：1.08至1.35，P<0.001）的风险。相反，我们发现基因预测的RA（OR：1.14，95%CI：1.05至1.24，P = 0.002）和SLE（OR：1.10，95%CI：1.03至1.17，P = 0.003）与患GD的较高风险相关。这些结果在欧洲队列中得到了部分验证。共定位分析表明GD与其他自身免疫性疾病之间可能存在共同的因果变异。特别是，基因ARID5B可能在自身免疫性疾病的发病中起重要作用。
本研究证实了GD与RA和SLE相关，并发现了一个可能的关键基因ARID5B。在临床实践中可能有必要加强检测以预防合并症的发生。
