Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study
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...
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MDPI AG
2023-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/9/2543 |
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| author | Baike Liu Zijian Qin Zhaolun Cai Zheran Liu Yun-Lin Chen Xiaonan Yin Yuan Yin Xingchen Peng Bo Zhang |
| author_facet | Baike Liu Zijian Qin Zhaolun Cai Zheran Liu Yun-Lin Chen Xiaonan Yin Yuan Yin Xingchen Peng Bo Zhang |
| author_sort | Baike Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T23:00:19Z |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T23:00:19Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-5d4c42e1abca4eadad7758f0528c2c1b2023-11-19T09:42:47ZengMDPI AGBiomedicines2227-90592023-09-01119254310.3390/biomedicines11092543Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization StudyBaike Liu0Zijian Qin1Zhaolun Cai2Zheran Liu3Yun-Lin Chen4Xiaonan Yin5Yuan Yin6Xingchen Peng7Bo Zhang8Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, ChinaGastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Cardiology, The 2nd Affiliated Hospital of Chongqing Medical University, Chongqing 400010, ChinaGastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, ChinaGastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, ChinaDepartment of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, ChinaGastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, ChinaBackground: 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.https://www.mdpi.com/2227-9059/11/9/2543inflammatory bowel diseaseCrohn’s diseaseulcerative colitisatherosclerotic cardiovascular diseasecoronary artery diseaseischemic stroke |
| spellingShingle | Baike Liu Zijian Qin Zhaolun Cai Zheran Liu Yun-Lin Chen Xiaonan Yin Yuan Yin Xingchen Peng Bo Zhang Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study Biomedicines inflammatory bowel disease Crohn’s disease ulcerative colitis atherosclerotic cardiovascular disease coronary artery disease ischemic stroke |
| title | Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study |
| title_full | Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study |
| title_fullStr | Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study |
| title_full_unstemmed | Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study |
| title_short | Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study |
| title_sort | evaluating the causal association between inflammatory bowel disease and risk of atherosclerotic cardiovascular disease univariable and multivariable mendelian randomization study |
| topic | inflammatory bowel disease Crohn’s disease ulcerative colitis atherosclerotic cardiovascular disease coronary artery disease ischemic stroke |
| url | https://www.mdpi.com/2227-9059/11/9/2543 |
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