孟德尔随机化研究炎症性肠病和 1 型糖尿病。
Mendelian randomization study of inflammatory bowel disease and type 1 diabetes.
机构信息
Department of Gastroenterology, First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
Department of Plastic Surgery, Changhai Hospital, Naval Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
出版信息
Endocrine. 2024 Dec;86(3):943-953. doi: 10.1007/s12020-024-03919-9. Epub 2024 Jul 31.
PURPOSE
Our purpose was to investigate and test the causal relationship between type 1 diabetes (T1D) and inflammatory bowel disease (IBD) and its major phenotypes, including ulcerative colitis (UC) and Crohn's disease (CD), in two large datasets.
METHODS
We obtained IBD samples from the largest publicly available genome-wide association study (GWAS), as well as the FinnGen database and the publicly accessible IEU GWAS database of T1D. We employed a two-sample Mendelian randomization approach to assess bidirectional causality using the inverse variance weighting (IVW) method as the primary outcome.
RESULTS
Genetic predisposition to T1D was associated with reduced risk of IBD (IVW: odds ratio (OR), 0.867; 95% confidence interval (CI), [0.852, 0.883]; P < 0.001), UC (OR = 0.879 [0.823, 0.939], P < 0.001), and CD (OR = 0.925 [0.872, 0.981], P = 0.009). The republication results found IBD genetically possessed negative association with T1D (OR = 0.781 [0.684, 0.891], P < 0.001). Additionally, a meta-analysis of results was conducted to prove the strong evidence between T1D and CD (OR = 0.95 [0.91, 0.98]; p = 0.01).
CONCLUSIONS
This study first demonstrated a causal effect of TID on the reduced risk of CD in the mendelian randomization study.
目的
我们旨在通过两项大型数据集，研究并验证 1 型糖尿病（T1D）与炎症性肠病（IBD）及其主要表型（包括溃疡性结肠炎（UC）和克罗恩病（CD））之间的因果关系。
方法
我们从最大的公开全基因组关联研究（GWAS）、芬兰基因（FinnGen）数据库以及可公开获取的 T1D 国际联盟 GWAS 数据库中获取 IBD 样本。我们采用两样本 Mendelian 随机化方法，使用逆方差加权（IVW）法作为主要结果，评估双向因果关系。
结果
T1D 的遗传易感性与 IBD（IVW：比值比（OR），0.867；95%置信区间（CI），[0.852，0.883]；P<0.001）、UC（OR=0.879 [0.823，0.939]，P<0.001）和 CD（OR=0.925 [0.872，0.981]，P=0.009）患病风险降低相关。再分析结果发现 IBD 与 T1D 呈负相关（OR=0.781 [0.684，0.891]，P<0.001）。此外，我们还进行了荟萃分析，以证明 T1D 与 CD 之间存在强关联（OR=0.95 [0.91，0.98]；p=0.01）。
结论
本研究首次在 Mendelian 随机化研究中证明了 TID 对 CD 患病风险降低的因果效应。
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