The Causal Relationship between Immune-Mediated Inflammatory Diseases and Aortic Aneurysm: A Bidirectional Two-Sample Mendelian Randomization Study

Background and Objective. Observational studies have frequently linked aortic aneurysm (AA) to immune-mediated inflammatory diseases (IMIDs) as a cardiovascular complication. However, the presence of confounding factors has cast doubt on the validity of this association and the potential for reverse...

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Main Authors: Sijia Sun, Jie Li, Mengxian Sun, Jie He, Songtao Tan, Ge Wang, Yuan Zheng, Xiaoping Fan
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2024/2474118
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author Sijia Sun
Jie Li
Mengxian Sun
Jie He
Songtao Tan
Ge Wang
Yuan Zheng
Xiaoping Fan
author_facet Sijia Sun
Jie Li
Mengxian Sun
Jie He
Songtao Tan
Ge Wang
Yuan Zheng
Xiaoping Fan
author_sort Sijia Sun
collection DOAJ
description Background and Objective. Observational studies have frequently linked aortic aneurysm (AA) to immune-mediated inflammatory diseases (IMIDs) as a cardiovascular complication. However, the presence of confounding factors has cast doubt on the validity of this association and the potential for reverse causality. This study employs a two-sample bidirectional Mendelian randomization (MR) approach to elucidate the causal relationships between AA and IMIDs. Methods. We sourced genetic association data from public genome-wide association study databases for populations of European ancestry. Adhering to MR principles, we identified valid instrumental variables from genetic variants. A range of statistical methods were applied for MR analysis, with the inverse variance weighted (IVW) method emerging as the most reliable estimator of causality in this context. Results. The causal estimates obtained using the IVW method revealed a significant association between genetically predicted AA and rheumatoid arthritis (RA; OR = 1.06, 95% CI = 1.01–1.12, P=0.029). Conversely, genetically predicted RA showed nonsignificant causal estimates of AA (OR = 0.97, 95% CI = 0.92–1.02, P=0.204). Additionally, there was no evidence to suggest that AA may increase the risk of inflammatory bowel disease (IBD), Crohn’s disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), and psoriasis (PSO). The sensitivity analysis confirmed the absence of heterogeneity or horizontal pleiotropy effects. Conclusion. Our findings shed light on the causal effects between genetically predisposed AA and RA. They also suggest the potential clinical utility of human leukocyte antigen (HLA) risk genetic markers for developing personalized treatment and prevention strategies.
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spelling doaj-art-d78eefde391b4f458d5b70788b4ded582025-02-03T11:49:27ZengWileyJournal of Immunology Research2314-71562024-01-01202410.1155/2024/2474118The Causal Relationship between Immune-Mediated Inflammatory Diseases and Aortic Aneurysm: A Bidirectional Two-Sample Mendelian Randomization StudySijia Sun0Jie Li1Mengxian Sun2Jie He3Songtao Tan4Ge Wang5Yuan Zheng6Xiaoping Fan7Second Clinical Medical CollegeSecond Clinical Medical CollegeDepartment of Cardiovascular SurgeryDepartment of Cardiovascular SurgeryDepartment of Cardiovascular SurgeryDepartment of Cardiovascular SurgeryDepartment of Cardiovascular SurgeryDepartment of Cardiovascular SurgeryBackground and Objective. Observational studies have frequently linked aortic aneurysm (AA) to immune-mediated inflammatory diseases (IMIDs) as a cardiovascular complication. However, the presence of confounding factors has cast doubt on the validity of this association and the potential for reverse causality. This study employs a two-sample bidirectional Mendelian randomization (MR) approach to elucidate the causal relationships between AA and IMIDs. Methods. We sourced genetic association data from public genome-wide association study databases for populations of European ancestry. Adhering to MR principles, we identified valid instrumental variables from genetic variants. A range of statistical methods were applied for MR analysis, with the inverse variance weighted (IVW) method emerging as the most reliable estimator of causality in this context. Results. The causal estimates obtained using the IVW method revealed a significant association between genetically predicted AA and rheumatoid arthritis (RA; OR = 1.06, 95% CI = 1.01–1.12, P=0.029). Conversely, genetically predicted RA showed nonsignificant causal estimates of AA (OR = 0.97, 95% CI = 0.92–1.02, P=0.204). Additionally, there was no evidence to suggest that AA may increase the risk of inflammatory bowel disease (IBD), Crohn’s disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), and psoriasis (PSO). The sensitivity analysis confirmed the absence of heterogeneity or horizontal pleiotropy effects. Conclusion. Our findings shed light on the causal effects between genetically predisposed AA and RA. They also suggest the potential clinical utility of human leukocyte antigen (HLA) risk genetic markers for developing personalized treatment and prevention strategies.http://dx.doi.org/10.1155/2024/2474118
spellingShingle Sijia Sun
Jie Li
Mengxian Sun
Jie He
Songtao Tan
Ge Wang
Yuan Zheng
Xiaoping Fan
The Causal Relationship between Immune-Mediated Inflammatory Diseases and Aortic Aneurysm: A Bidirectional Two-Sample Mendelian Randomization Study
Journal of Immunology Research
title The Causal Relationship between Immune-Mediated Inflammatory Diseases and Aortic Aneurysm: A Bidirectional Two-Sample Mendelian Randomization Study
title_full The Causal Relationship between Immune-Mediated Inflammatory Diseases and Aortic Aneurysm: A Bidirectional Two-Sample Mendelian Randomization Study
title_fullStr The Causal Relationship between Immune-Mediated Inflammatory Diseases and Aortic Aneurysm: A Bidirectional Two-Sample Mendelian Randomization Study
title_full_unstemmed The Causal Relationship between Immune-Mediated Inflammatory Diseases and Aortic Aneurysm: A Bidirectional Two-Sample Mendelian Randomization Study
title_short The Causal Relationship between Immune-Mediated Inflammatory Diseases and Aortic Aneurysm: A Bidirectional Two-Sample Mendelian Randomization Study
title_sort causal relationship between immune mediated inflammatory diseases and aortic aneurysm a bidirectional two sample mendelian randomization study
url http://dx.doi.org/10.1155/2024/2474118
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