Causal associations of Sjögren's syndrome with cardiovascular disease: A two-sample Mendelian randomization study

Study objectives: Observational and cohort studies have associated Sjögren's syndrome (SS) with various types of cardiovascular disease (CVD), yet causal relationships have not been established. We employed Mendelian randomization (MR) to investigate potential causal links between SS and CVD in...

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Main Authors: Chen Su, Xiaobo Zhu, Qiang Wang, Feng Jiang, Junjie Zhang
Format: Article
Language:English
Published: Elsevier 2024-11-01
Series:American Heart Journal Plus
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666602224001253
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author Chen Su
Xiaobo Zhu
Qiang Wang
Feng Jiang
Junjie Zhang
author_facet Chen Su
Xiaobo Zhu
Qiang Wang
Feng Jiang
Junjie Zhang
author_sort Chen Su
collection DOAJ
description Study objectives: Observational and cohort studies have associated Sjögren's syndrome (SS) with various types of cardiovascular disease (CVD), yet causal relationships have not been established. We employed Mendelian randomization (MR) to investigate potential causal links between SS and CVD in the general population. Methods: We conducted a two-sample MR analysis using data from four distinct sources for 11 genome-wide significant single nucleotide polymorphisms (SNPs) associated with SS and data for 13 types of CVD sourced from FinnGen, IEU OpenGWAS, and GWAS catalog. The inverse variance weighted method was selected as the primary analytical approach, complemented by various sensitivity analyses. Results: MR analyses provide evidence of a significantly increased risk of ischemic stroke associated with genetically predicted SS (odds ratio [OR], 1.0237; 95 % CI, 1.0096 to 1.0379; p = 0.0009), as well as suggestive evidence of a potential causal relationship between SS and an increased risk of chronic heart failure (OR, 1.0302; 95 % CI, 1.0020 to 1.0592; p = 0.0355). Sensitivity analyses reinforced these associations, demonstrating robustness and consistency across multiple statistical methods. The secondary analysis, conducted after outlier correction using MR-PRESSO and RadialMR methods, reaffirmed these associations and also indicated a suggestive causal link between SS and non-rheumatic valvular heart disease (OR, 1.0251; 95 % CI, 1.0021 to 1.0486; p = 0.0323). Conclusions: This study demonstrates that genetically predicted SS is a potential causative risk factor for ischemic stroke, chronic heart failure, and non-rheumatic valvular heart disease on a large-scale population. However, further research incorporating ancestral diversity is required to confirm a causal relationship between SS and CVD.
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spelling doaj-art-f29e577d6ca24865bcbba22db96329e22024-11-14T04:32:51ZengElsevierAmerican Heart Journal Plus2666-60222024-11-0147100482Causal associations of Sjögren's syndrome with cardiovascular disease: A two-sample Mendelian randomization studyChen Su0Xiaobo Zhu1Qiang Wang2Feng Jiang3Junjie Zhang4Department of Cardiothoracic Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu Province, China; Department of Cardiothoracic Surgery, Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu Province, ChinaDepartment of Cardiothoracic Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu Province, China; Department of Cardiothoracic Surgery, Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu Province, ChinaDepartment of Cardiothoracic Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu Province, China; Department of Cardiothoracic Surgery, Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu Province, ChinaDepartment of Cardiothoracic Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu Province, China; Department of Cardiothoracic Surgery, Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu Province, ChinaCorresponding author at: No. 2 North Yongning Road, Changzhou, Jiangsu Province 213000, China.; Department of Cardiothoracic Surgery, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu Province, China; Department of Cardiothoracic Surgery, Wujin Clinical College of Xuzhou Medical University, Changzhou, Jiangsu Province, ChinaStudy objectives: Observational and cohort studies have associated Sjögren's syndrome (SS) with various types of cardiovascular disease (CVD), yet causal relationships have not been established. We employed Mendelian randomization (MR) to investigate potential causal links between SS and CVD in the general population. Methods: We conducted a two-sample MR analysis using data from four distinct sources for 11 genome-wide significant single nucleotide polymorphisms (SNPs) associated with SS and data for 13 types of CVD sourced from FinnGen, IEU OpenGWAS, and GWAS catalog. The inverse variance weighted method was selected as the primary analytical approach, complemented by various sensitivity analyses. Results: MR analyses provide evidence of a significantly increased risk of ischemic stroke associated with genetically predicted SS (odds ratio [OR], 1.0237; 95 % CI, 1.0096 to 1.0379; p = 0.0009), as well as suggestive evidence of a potential causal relationship between SS and an increased risk of chronic heart failure (OR, 1.0302; 95 % CI, 1.0020 to 1.0592; p = 0.0355). Sensitivity analyses reinforced these associations, demonstrating robustness and consistency across multiple statistical methods. The secondary analysis, conducted after outlier correction using MR-PRESSO and RadialMR methods, reaffirmed these associations and also indicated a suggestive causal link between SS and non-rheumatic valvular heart disease (OR, 1.0251; 95 % CI, 1.0021 to 1.0486; p = 0.0323). Conclusions: This study demonstrates that genetically predicted SS is a potential causative risk factor for ischemic stroke, chronic heart failure, and non-rheumatic valvular heart disease on a large-scale population. However, further research incorporating ancestral diversity is required to confirm a causal relationship between SS and CVD.http://www.sciencedirect.com/science/article/pii/S2666602224001253Sjögren's syndromeCardiovascular diseaseMendelian randomizationSingle-nucleotide polymorphismsFinnGen
spellingShingle Chen Su
Xiaobo Zhu
Qiang Wang
Feng Jiang
Junjie Zhang
Causal associations of Sjögren's syndrome with cardiovascular disease: A two-sample Mendelian randomization study
American Heart Journal Plus
Sjögren's syndrome
Cardiovascular disease
Mendelian randomization
Single-nucleotide polymorphisms
FinnGen
title Causal associations of Sjögren's syndrome with cardiovascular disease: A two-sample Mendelian randomization study
title_full Causal associations of Sjögren's syndrome with cardiovascular disease: A two-sample Mendelian randomization study
title_fullStr Causal associations of Sjögren's syndrome with cardiovascular disease: A two-sample Mendelian randomization study
title_full_unstemmed Causal associations of Sjögren's syndrome with cardiovascular disease: A two-sample Mendelian randomization study
title_short Causal associations of Sjögren's syndrome with cardiovascular disease: A two-sample Mendelian randomization study
title_sort causal associations of sjogren s syndrome with cardiovascular disease a two sample mendelian randomization study
topic Sjögren's syndrome
Cardiovascular disease
Mendelian randomization
Single-nucleotide polymorphisms
FinnGen
url http://www.sciencedirect.com/science/article/pii/S2666602224001253
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