Xie Weidong, Jiang Haojie, Chen Yao, Yu Zhaojie, Song Yaoyu, Zhang Huanhao, Li Sen, Han Shaoliang, Liu Naxin
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Graduate School, Zhejiang University, Hangzhou, China.
Front Genet. 2024 Sep 16;15:1335839. doi: 10.3389/fgene.2024.1335839. eCollection 2024.
Previous studies have suggested an association between Type 1 diabetes (T1D) and autoimmune diseases (AIDs), but the causal relationship remains unclear. Therefore, this study utilizes publicly available Genome-Wide Association Studies (GWAS) databases and employs a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between T1D and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD).
Summary GWAS data for T1D, SLE, RA, and IBD were downloaded from open GWAS databases and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We employed a series of methods to select instrumental variables closely related to T1D. To enhance the reliability of our conclusions, we applied multiple robust analytical methods, with the inverse variance weighted (IVW) method as the primary approach. Validation and meta-analysis were conducted using the FinnGen consortium. Additionally, we assessed heterogeneity, pleiotropy, and sensitivity to ensure the robustness of our conclusions.
A potential causal association was found between T1D and SLE (OR = 1.37, 95% CI = 1.26 - 1.49, P < 0.001), which was further confirmed by meta-analysis. Similarly, a potential causal association was found between T1D and RA (OR = 1.32, 95% CI = 1.17 - 1.50, P < 0.001), and this was also confirmed by meta-analysis. Although the association between T1D and IBD showed P < 0.05, the leave-one-out test did not pass, and further meta-analysis indicated no significant statistical association between them.
Our study reveals the relationships between T1D and three clinically common autoimmune diseases (SLE, RA, and IBD). This research supplements previous studies and provides a reference for future clinical work.
先前的研究表明1型糖尿病（T1D）与自身免疫性疾病（AIDs）之间存在关联，但因果关系仍不明确。因此，本研究利用公开可用的全基因组关联研究（GWAS）数据库，并采用两样本孟德尔随机化（MR）方法来探索T1D与系统性红斑狼疮（SLE）、类风湿性关节炎（RA）和炎症性肠病（IBD）之间的因果关系。
从开放的GWAS数据库和国际炎症性肠病遗传学联盟（IIBDGC）下载了T1D、SLE、RA和IBD的汇总GWAS数据。我们采用了一系列方法来选择与T1D密切相关的工具变量。为了提高我们结论的可靠性，我们应用了多种稳健的分析方法，以逆方差加权（IVW）方法作为主要方法。使用芬兰基因组联盟进行验证和荟萃分析。此外，我们评估了异质性、多效性和敏感性，以确保我们结论的稳健性。
发现T1D与SLE之间存在潜在的因果关联（OR = 1.37，95% CI = 1.26 - 1.49，P < 0.001），荟萃分析进一步证实了这一点。同样，发现T1D与RA之间存在潜在的因果关联（OR = 1.32，95% CI = 1.17 - 1.50，P < 0.001），这也得到了荟萃分析的确证。尽管T1D与IBD之间的关联显示P < 0.05，但留一法检验未通过，进一步的荟萃分析表明它们之间无显著的统计学关联。
我们的研究揭示了T1D与三种临床常见的自身免疫性疾病（SLE、RA和IBD）之间的关系。本研究补充了先前的研究，并为未来的临床工作提供了参考。
