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炎症性肠病与憩室病之间不存在双向关系:一项遗传相关性和孟德尔随机化研究。

No bidirectional relationship between inflammatory bowel disease and diverticular disease: a genetic correlation and Mendelian randomization study.

作者信息

Aierken Ailikamu, Atabieke Falide, Aierken Munire, Li Jian, Xia Yu, Aizezi Yierzhati, Li Shui-Xue

机构信息

Graduate School of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi, China.

The Second Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

出版信息

Front Genet. 2024 Feb 14;15:1334473. doi: 10.3389/fgene.2024.1334473. eCollection 2024.

Abstract

Although previous studies found that inflammatory bowel disease (IBD) and diverticular disease (DD) usually co-exist clinically, studies examining the relationship are spare. Our study aspires to investigate the causal correlation between the IBD [including ulcerative colitis (UC) and Crohn's disease (CD)] and DD using the Mendelian randomization (MR) analysis. We conducted a two-sample bidirectional MR analysis using publicly available genome-wide association studies (GWAS) summary data. The single nucleotide polymorphism (SNP) data associated with DD and IBD were obtained from the Finnish Biobank and UK Biobank, respectively. Through secondary data analysis of all GWAS summary data, we systematically screened genetic instrumental variables. To address the impact of horizontal pleiotropy, several methods were employed, including the inverse variance-weighted method (IVW), maximum likelihood method, Egger regression method, weighted median method, and simple median method. These approaches aimed to detect and correct for the potential bias caused by horizontal pleiotropy. Genetically predicted DD did not have a causal effect on IBD (OR 1.06, 95% CI 0.98-1.17, = 0.15), and had no causal effect on UC (OR 1.10, 95% CI 0.94-1.20, = 0.36) and CD (OR 1.03, 95% CI 0.92-1.16, = 0.62) either. Furthermore, in the reverse MR analysis, we did not observe any significant causal effect of IBD on DD. Results of complementary methods showed consistent results with those of the IVW method. This study's findings do not provide evidence for a causal relationship between IBD and DD, which contradicts the majority of observational studies.

摘要

尽管先前的研究发现炎症性肠病(IBD)和憩室病(DD)在临床上通常共存,但对两者关系的研究却很少。我们的研究旨在使用孟德尔随机化(MR)分析来研究IBD[包括溃疡性结肠炎(UC)和克罗恩病(CD)]与DD之间的因果关系。我们使用公开可用的全基因组关联研究(GWAS)汇总数据进行了两样本双向MR分析。与DD和IBD相关的单核苷酸多态性(SNP)数据分别从芬兰生物银行和英国生物银行获得。通过对所有GWAS汇总数据进行二次数据分析,我们系统地筛选了遗传工具变量。为了解决水平多效性的影响,我们采用了几种方法,包括逆方差加权法(IVW)、最大似然法、Egger回归法、加权中位数法和简单中位数法。这些方法旨在检测和纠正由水平多效性引起的潜在偏差。遗传预测的DD对IBD没有因果效应(OR = 1.06,95%CI = 0.98 - 1.17,P = 0.15),对UC(OR = 1.10,95%CI = 0.94 - 1.20,P = 0.36)和CD(OR = 1.03,95%CI = 0.92 - 1.16,P = 0.62)也没有因果效应。此外,在反向MR分析中,我们没有观察到IBD对DD有任何显著的因果效应。补充方法的结果与IVW方法的结果一致。本研究结果并未为IBD与DD之间的因果关系提供证据,这与大多数观察性研究结果相矛盾。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d2e/10899511/13bb62ce1beb/fgene-15-1334473-g001.jpg

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