Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study

作者全名："Liu, Baike; Qin, Zijian; Cai, Zhaolun; Liu, Zheran; Chen, Yun-Lin; Yin, Xiaonan; Yin, Yuan; Peng, Xingchen; Zhang, Bo"

作者地址："[Liu, Baike; Cai, Zhaolun; Yin, Xiaonan; Yin, Yuan; Zhang, Bo] Sichuan Univ, West China Hosp, Gastr Canc Ctr, Dept Gen Surg, Chengdu 610041, Peoples R China; [Liu, Baike; Cai, Zhaolun; Yin, Xiaonan; Yin, Yuan; Zhang, Bo] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Peoples R China; [Liu, Baike; Cai, Zhaolun; Yin, Xiaonan; Yin, Yuan; Zhang, Bo] Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Canc Ctr, Chengdu 610041, Peoples R China; [Qin, Zijian; Liu, Zheran; Peng, Xingchen] Sichuan Univ, West China Hosp, Dept Biotherapy, Canc Ctr, Chengdu 610041, Peoples R China; [Chen, Yun-Lin] Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China"

通信作者："Zhang, B (通讯作者)，Sichuan Univ, West China Hosp, Gastr Canc Ctr, Dept Gen Surg, Chengdu 610041, Peoples R China.; Zhang, B (通讯作者)，Sichuan Univ, State Key Lab Biotherapy, Chengdu 610041, Peoples R China.; Zhang, B (通讯作者)，Sichuan Univ, West China Hosp, Natl Clin Res Ctr Geriatr, Canc Ctr, Chengdu 610041, Peoples R China.; Peng, XC (通讯作者)，Sichuan Univ, West China Hosp, Dept Biotherapy, Canc Ctr, Chengdu 610041, Peoples R China."

来源：BIOMEDICINES

ESI学科分类：　

WOS号：WOS:001071371400001

JCR分区：Q1

影响因子：3.9

年份：2023

卷号：11

期号：9

开始页：　

结束页：　

文献类型：Article

关键词：inflammatory bowel disease; Crohn's disease; ulcerative colitis; atherosclerotic cardiovascular disease; coronary artery disease; ischemic stroke; Mendelian randomization study

摘要："Background: Observational studies suggested that inflammatory bowel disease (IBD) (i.e., Crohn's disease [CD] and ulcerative colitis [UC]) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease (CAD) and ischemic stroke. However, it is still unclear whether the observed associations causally exist. Thus, we aim to examine the potential effect of IBD, CD, and UC on the risk of CAD and ischemic stroke, using a two-sample Mendelian randomization (MR) study. Methods: Genetic instruments for IBD, CD, and UC were retrieved from the latest published genome-wide association studies (GWASs) of European ancestry. GWAS summary data for instrument-outcome associations were gathered from four independent resources: CARDIoGRAMplusC4D Consortium, MEGASTROKE consortium, FinnGen, and UK Biobank. The inverse variance weighted (IVW) method and multiple pleiotropy-robust approaches were conducted and, subsequently, combined in a fixed-effect meta-analysis. Moreover, multivariable MR (MVMR) analysis was conducted to adjust for potential influencing instrumental variables. Results: The IVW method revealed no causal effect of IBD on the risk of CAD (overall IBD on CAD: OR 1.003, 95%CI 0.982 to 1.025; CD on CAD: OR 0.997, 95%CI 0.978 to 1.016; UC on CAD: OR 0.986, 95%CI 0.963 to 1.010) or the risk of ischemic stroke (overall IBD on ischemic stroke: OR 0.994, 95%CI 0.970 to 1.018; CD on ischemic stroke: OR 0.996, 95%CI 0.979 to 1.014; UC on ischemic stroke: OR 0.999, 95%CI 0.978 to 1.020). The results of the meta-analysis and MVMR remained consistent. Conclusion: Our MR analysis does not support a causal effect of IBD on CAD and ischemic stroke, and previous results from observational studies might be biased through uncontrolled confoundings (such as IBD-specific medications and detection bias, etc.) that warrant further research."

基金机构："Worldwide investigators contributed data on IBD, CAD, and ischemic stroke from different consortiums. Thank you to all the investigators who have made their GWAS data available, and to researchers from the FinnGen project and Neale Lab."

基金资助正文："Worldwide investigators contributed data on IBD, CAD, and ischemic stroke from different consortiums. Thank you to all the investigators who have made their GWAS data available, and to researchers from the FinnGen project and Neale Lab."