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2 型糖尿病与炎症性肠病:一项双向两样本 Mendelian 随机研究。

Type 2 diabetes and inflammatory bowel disease: a bidirectional two-sample Mendelian randomization study.

机构信息

School of Nursing, Qingdao University, Qingdao, 266071, China.

Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.

出版信息

Sci Rep. 2024 Mar 1;14(1):5149. doi: 10.1038/s41598-024-55869-x.

Abstract

To investigate the association between T2DM and IBD by bidirectional two-sample Mendelian randomization (MR) to clarify the casual relationship. Independent genetic variants for T2DM and IBD were selected as instruments from published genome-wide association studies (GWAS), mainly in European ancestry. Instrumental variables (IVs) associated with T2DM and IBD were extracted separately from the largest GWAS meta-analysis. MR analyses included inverse variance weighting, weighted median estimator, MR Egger regression, and sensitivity analyses with Steiger filtering and MR PRESSO. In the data samples for Ulcerative colitis (UC) (6968 cases, 20,464 controls) and Crohn's disease (CD) (5956 cases, 14,927 controls), there was a negative causal relationship between T2DM and UC [IVW, OR/95%CI: 0.882/(0.826,0.942), p < 0.001]. However, the causal relationships between T2DM and CD, UC and T2DM, CD and T2DM were not significant, and the p value measured by the IVW method was ≥ 0.05. All SNPs showed no significant horizontal pleiotropy (p > 0.05). The results of the bidirectional MR Study suggest that T2DM has a negative causal effect on UC, which provides implications for clinical treatment decisions in IBD patients with T2DM. The findings do not support a causal relationship between T2DM and CD, UC and T2DM, or CD and T2DM, and the impact of IBD on T2DM needs further investigation.

摘要

为了通过双向两样本孟德尔随机化(MR)研究来探究 T2DM 和 IBD 之间的关联,以明确其因果关系。我们从已发表的全基因组关联研究(GWAS)中选择了用于 T2DM 和 IBD 的独立遗传变异作为工具变量(IVs),这些研究主要基于欧洲血统人群。我们分别从最大的 GWAS 荟萃分析中提取与 T2DM 和 IBD 相关的工具变量。MR 分析包括逆方差加权、加权中位数估计、MR Egger 回归以及使用 Steiger 过滤和 MR PRESSO 的敏感性分析。在溃疡性结肠炎(UC)(6968 例病例,20464 例对照)和克罗恩病(CD)(5956 例病例,14927 例对照)的数据样本中,T2DM 和 UC 之间存在负向因果关系[IVW,OR/95%CI:0.882/(0.826,0.942),p<0.001]。然而,T2DM 和 CD、UC 和 T2DM、CD 和 T2DM 之间的因果关系并不显著,且 IVW 法测量的 p 值≥0.05。所有 SNP 均未显示出显著的水平遗传异质性(p>0.05)。双向 MR 研究的结果表明,T2DM 对 UC 具有负向因果效应,这为 IBD 合并 T2DM 患者的临床治疗决策提供了启示。这些发现不支持 T2DM 与 CD、UC 和 T2DM 或 CD 和 T2DM 之间存在因果关系,并且需要进一步研究 IBD 对 T2DM 的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8dc5/10907708/d8450dcd4d67/41598_2024_55869_Fig1_HTML.jpg

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