Genetic association between immune-mediated inflammatory diseases and peripheral artery disease: a Mendelian randomization study

Abstract Several observational studies have revealed that immune-mediated inflammatory diseases (IMIDs) are associated with an increased risk of peripheral artery disease (PAD). However, the causal association remains to be determined. To corroborate previous research, we conducted Mendelian randomi...

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Main Authors: Haichao Wu, Dandan Zheng, Long Zhou, Qiang Wang, Tao Wang, Siyuan Liang
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-82987-3
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author Haichao Wu
Dandan Zheng
Long Zhou
Qiang Wang
Tao Wang
Siyuan Liang
author_facet Haichao Wu
Dandan Zheng
Long Zhou
Qiang Wang
Tao Wang
Siyuan Liang
author_sort Haichao Wu
collection DOAJ
description Abstract Several observational studies have revealed that immune-mediated inflammatory diseases (IMIDs) are associated with an increased risk of peripheral artery disease (PAD). However, the causal association remains to be determined. To corroborate previous research, we conducted Mendelian randomization (MR) analysis with the aim of clarifying the associations of various IMIDs with PAD. two-sample MR analysis was conducted to investigate the potential causal association between eight common IMIDs (including rheumatoid arthritis (RA), Crohn’s disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), ankylosing spondylitis(AS), psoriasis(PSO), multiple sclerosis(MS), and hashimoto thyroiditis(HT)) and PAD. Genome-wide association study (GWAS) was used to identify genetic variants associated with IMIDs and PAD. We employed the inverse variance weighted (IVW) method as the primary method to verify the causal relationship between exposures (IMIDs) and outcomes (PAD). In addition, heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis were performed to evaluate the robustness of the MR results. The IVW model yielded evidence of a positive association between RA and PAD (OR = 1.059, 95% CI: 1.026–1.094, p<0.001), which was consistent with the results obtained from MR-Egger regression and weighted median analyses, indicating that the results of MR analysis were reliable. However, no statistically significant associations were observed between other IMIDs, including UC, CD, SLE, AS, PSO, MS, and HT, and PAD. Our analysis supported the causal association of RA with increased risks of PAD. Strengthening screening and prevention of PAD is of great significance in reducing the risk of PAD in populations with RA.
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spelling doaj-art-a0f07432036942f8b8d1e194ea8118122025-02-02T12:20:15ZengNature PortfolioScientific Reports2045-23222025-01-011511710.1038/s41598-024-82987-3Genetic association between immune-mediated inflammatory diseases and peripheral artery disease: a Mendelian randomization studyHaichao Wu0Dandan Zheng1Long Zhou2Qiang Wang3Tao Wang4Siyuan Liang5Department of Vascular Surgery, Taizhou Municipal HospitalFaculty of Nursing, Mahidol UniversityDepartment of Vascular Surgery, Taizhou Municipal HospitalDepartment of Vascular Surgery, Taizhou Municipal HospitalDepartment of Vascular Surgery, Taizhou Municipal HospitalDepartment of Vascular Surgery, Taizhou Municipal HospitalAbstract Several observational studies have revealed that immune-mediated inflammatory diseases (IMIDs) are associated with an increased risk of peripheral artery disease (PAD). However, the causal association remains to be determined. To corroborate previous research, we conducted Mendelian randomization (MR) analysis with the aim of clarifying the associations of various IMIDs with PAD. two-sample MR analysis was conducted to investigate the potential causal association between eight common IMIDs (including rheumatoid arthritis (RA), Crohn’s disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), ankylosing spondylitis(AS), psoriasis(PSO), multiple sclerosis(MS), and hashimoto thyroiditis(HT)) and PAD. Genome-wide association study (GWAS) was used to identify genetic variants associated with IMIDs and PAD. We employed the inverse variance weighted (IVW) method as the primary method to verify the causal relationship between exposures (IMIDs) and outcomes (PAD). In addition, heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis were performed to evaluate the robustness of the MR results. The IVW model yielded evidence of a positive association between RA and PAD (OR = 1.059, 95% CI: 1.026–1.094, p<0.001), which was consistent with the results obtained from MR-Egger regression and weighted median analyses, indicating that the results of MR analysis were reliable. However, no statistically significant associations were observed between other IMIDs, including UC, CD, SLE, AS, PSO, MS, and HT, and PAD. Our analysis supported the causal association of RA with increased risks of PAD. Strengthening screening and prevention of PAD is of great significance in reducing the risk of PAD in populations with RA.https://doi.org/10.1038/s41598-024-82987-3Peripheral artery diseaseImmune-mediated inflammatory diseasesMendelian randomizationGenetic associationRheumatoid arthritis
spellingShingle Haichao Wu
Dandan Zheng
Long Zhou
Qiang Wang
Tao Wang
Siyuan Liang
Genetic association between immune-mediated inflammatory diseases and peripheral artery disease: a Mendelian randomization study
Scientific Reports
Peripheral artery disease
Immune-mediated inflammatory diseases
Mendelian randomization
Genetic association
Rheumatoid arthritis
title Genetic association between immune-mediated inflammatory diseases and peripheral artery disease: a Mendelian randomization study
title_full Genetic association between immune-mediated inflammatory diseases and peripheral artery disease: a Mendelian randomization study
title_fullStr Genetic association between immune-mediated inflammatory diseases and peripheral artery disease: a Mendelian randomization study
title_full_unstemmed Genetic association between immune-mediated inflammatory diseases and peripheral artery disease: a Mendelian randomization study
title_short Genetic association between immune-mediated inflammatory diseases and peripheral artery disease: a Mendelian randomization study
title_sort genetic association between immune mediated inflammatory diseases and peripheral artery disease a mendelian randomization study
topic Peripheral artery disease
Immune-mediated inflammatory diseases
Mendelian randomization
Genetic association
Rheumatoid arthritis
url https://doi.org/10.1038/s41598-024-82987-3
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