Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions

Backgroud: Autoimmune diseases (AIDs) have been associated with various cardiovascular diseases (CVDs) in observational data. However, the causality of these associations remains uncertain. Therefore, a systematic assessment of the impact of AIDS on cardiovascular risk is required. Results: We asses...

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Main Authors: Yulin Bao, Lingfeng Gu, Jiayi Chen, Hao Wang, Zemu Wang, Huijuan Wang, Sibo Wang, Liansheng Wang
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Journal of Translational Autoimmunity
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589909024000297
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author Yulin Bao
Lingfeng Gu
Jiayi Chen
Hao Wang
Zemu Wang
Huijuan Wang
Sibo Wang
Liansheng Wang
author_facet Yulin Bao
Lingfeng Gu
Jiayi Chen
Hao Wang
Zemu Wang
Huijuan Wang
Sibo Wang
Liansheng Wang
author_sort Yulin Bao
collection DOAJ
description Backgroud: Autoimmune diseases (AIDs) have been associated with various cardiovascular diseases (CVDs) in observational data. However, the causality of these associations remains uncertain. Therefore, a systematic assessment of the impact of AIDS on cardiovascular risk is required. Results: We assessed the impact of 19 common AIDs on 14 CVDs using bidirectional Mendelian randomization (MR). Celiac disease (odds ratio [OR] = 2.949, 95 % confidence interval [CI]: 1.111–7.827, P = 0.030) and type 1 diabetes mellitus (T1DM) (OR = 1.044, 95 % CI: 1.021–1.068, P = 1.82e-4) were associated with an increased risk of peripheral arterial disease (PAD). Additionally, celiac disease was linked to an increased risk of arrhythmia (OR = 1.008, 95 % CI: 1.002–1.013, P = 0.004), multiple sclerosis to venous thromboembolism (OR = 1.001, 95 % CI: 1.000–1.001, P = 0.010), and psoriasis to heart failure (OR = 1.048, 95 % CI: 1.021–1.077, P = 0.001). Sensitivity analyses were conducted to enhance the robustness of these findings. Predominantly, immune response and inflammation-related pathways were enriched in the aforementioned associations. Mediation analysis identified human leukocyte antigen-DR positive myeloid dendritic cells as partially mediating the effect of T1DM on PAD, with a mediated proportion of 16.61 % (P = 0.028). Potential therapeutic agents, such as tumor necrosis factor-alpha inhibitors and interferon, may have efficacy in treating AID-related CVDs. Conclusions: This study presents genetic evidence of certain AIDs impacting specific CVDs and identifies potential mediators and drugs.
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spelling doaj-art-5d4384655bd644fa8a3fea890b0ca4e02025-08-20T01:59:34ZengElsevierJournal of Translational Autoimmunity2589-90902024-12-01910025910.1016/j.jtauto.2024.100259Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditionsYulin Bao0Lingfeng Gu1Jiayi Chen2Hao Wang3Zemu Wang4Huijuan Wang5Sibo Wang6Liansheng Wang7Department of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, 210029, ChinaDepartment of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, 210029, ChinaDepartment of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, 210029, ChinaDepartment of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, 210029, ChinaDepartment of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, 210029, ChinaDepartment of Immunology, School of Basic Medical Science, Nanjing Medical University, Nanjing, Jiangsu, 211166, ChinaDepartment of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, 210029, ChinaDepartment of Cardiology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, Jiangsu, 210029, China; Corresponding author.Backgroud: Autoimmune diseases (AIDs) have been associated with various cardiovascular diseases (CVDs) in observational data. However, the causality of these associations remains uncertain. Therefore, a systematic assessment of the impact of AIDS on cardiovascular risk is required. Results: We assessed the impact of 19 common AIDs on 14 CVDs using bidirectional Mendelian randomization (MR). Celiac disease (odds ratio [OR] = 2.949, 95 % confidence interval [CI]: 1.111–7.827, P = 0.030) and type 1 diabetes mellitus (T1DM) (OR = 1.044, 95 % CI: 1.021–1.068, P = 1.82e-4) were associated with an increased risk of peripheral arterial disease (PAD). Additionally, celiac disease was linked to an increased risk of arrhythmia (OR = 1.008, 95 % CI: 1.002–1.013, P = 0.004), multiple sclerosis to venous thromboembolism (OR = 1.001, 95 % CI: 1.000–1.001, P = 0.010), and psoriasis to heart failure (OR = 1.048, 95 % CI: 1.021–1.077, P = 0.001). Sensitivity analyses were conducted to enhance the robustness of these findings. Predominantly, immune response and inflammation-related pathways were enriched in the aforementioned associations. Mediation analysis identified human leukocyte antigen-DR positive myeloid dendritic cells as partially mediating the effect of T1DM on PAD, with a mediated proportion of 16.61 % (P = 0.028). Potential therapeutic agents, such as tumor necrosis factor-alpha inhibitors and interferon, may have efficacy in treating AID-related CVDs. Conclusions: This study presents genetic evidence of certain AIDs impacting specific CVDs and identifies potential mediators and drugs.http://www.sciencedirect.com/science/article/pii/S2589909024000297Autoimmune diseasesCardiovascular riskMendelian randomization
spellingShingle Yulin Bao
Lingfeng Gu
Jiayi Chen
Hao Wang
Zemu Wang
Huijuan Wang
Sibo Wang
Liansheng Wang
Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions
Journal of Translational Autoimmunity
Autoimmune diseases
Cardiovascular risk
Mendelian randomization
title Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions
title_full Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions
title_fullStr Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions
title_full_unstemmed Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions
title_short Autoimmune diseases and cardiovascular risk: Mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions
title_sort autoimmune diseases and cardiovascular risk mendelian randomization analysis for the impact of 19 autoimmune diseases on 14 cardiovascular conditions
topic Autoimmune diseases
Cardiovascular risk
Mendelian randomization
url http://www.sciencedirect.com/science/article/pii/S2589909024000297
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