Multiple Sclerosis and the Risk of Cardiovascular Diseases: A Mendelian Randomization Study

被引:20
作者
Yang, Fangkun [1 ,2 ,3 ]
Hu, Teng [4 ]
He, Kewan [4 ]
Ying, Jiajun [1 ]
Cui, Hanbin [3 ]
机构
[1] Zhejiang Univ, Ningbo Hosp, Sch Med, Ningbo, Peoples R China
[2] Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Cardiol, Hangzhou, Peoples R China
[3] Ningbo Univ, Ningbo Hosp 1, Cardiol Ctr, Ningbo, Peoples R China
[4] Ningbo Univ, Ningbo Hosp 1, Sch Med, Ningbo, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
关键词
multiple sclerosis; cardiovascular disease; Mendelian randomization; genome-wide association studies; causal association; ENDOTHELIAL DYSFUNCTION; VASCULAR COMORBIDITIES; CAUSAL INFERENCE; HEART; METAANALYSIS; INSTRUMENTS; MECHANISMS; STROKE; STATE; POWER;
D O I
10.3389/fimmu.2022.861885
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
BackgroundObservational studies suggested that multiple sclerosis (MS) is associated with cardiovascular diseases (CVDs). However, the causal association has not been fully elucidated. Thus, we aim to assess the causality of the associations of MS with risk of CVDs. MethodsA two-sample Mendelian randomization (MR) study was performed to explore the causality. Genetic instruments were identified for MS from a genome-wide association study (GWAS) involving 115,803 individuals. Summary-level data for CVDs were obtained from different GWAS meta-analysis studies. MR analysis was conducted mainly using the inverse-variance weighted (IVW) method. Sensitivity analyses were further performed to ensure the robustness of the results. ResultsThis MR study found suggestive evidence that genetic liability to MS was associated with an increased risk of coronary artery disease (CAD) [odds ratio (OR), 1.02; 95% confidence interval (CI), 1.00-1.04; p = 0.03], myocardial infarction (MI) (OR, 1.03; 95% CI, 1.00-1.06; p = 0.01), heart failure (HF) (OR, 1.02; 95% CI, 1.00-1.04; p = 0.02), all-cause stroke (AS) (OR, 1.02; 95% CI, 1.00-1.05; p = 0.02), and any ischemic stroke (AIS) (OR, 1.02; 95% CI, 1.00-1.05; p = 0.04). The null-association was observed between MS and the other CVDs. Further analyses found little evidence of pleiotropy. ConclusionsWe provided suggestive genetic evidence for the causal associations of MS with increased risk of CAD, MI, HF, AS, and AIS, which highlighted the significance of active monitoring and prevention of cardiovascular risk to combat cardiovascular comorbidities in MS patients.
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页数:7
相关论文
共 52 条
[1]   Coagulation status and biochemical and inflammatory markers in multiple sclerosis [J].
Aksungar, Fehime B. ;
Topkaya, Aynur E. ;
Yildiz, Zeynep ;
Sahin, Sevkl ;
Turk, Ulku .
JOURNAL OF CLINICAL NEUROSCIENCE, 2008, 15 (04) :393-397
[2]   Stress resilience in male adolescents and subsequent stroke risk: cohort study [J].
Bergh, Cecilia ;
Udumyan, Ruzan ;
Fall, Katja ;
Nilsagard, Ylva ;
Appelros, Peter ;
Montgomery, Scott .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2014, 85 (12) :1331-1336
[3]   Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator [J].
Bowden, Jack ;
Smith, George Davey ;
Haycock, Philip C. ;
Burgess, Stephen .
GENETIC EPIDEMIOLOGY, 2016, 40 (04) :304-314
[4]   Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression [J].
Bowden, Jack ;
Smith, George Davey ;
Burgess, Stephen .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2015, 44 (02) :512-525
[5]   Calculating statistical power in Mendelian randomization studies [J].
Brion, Marie-Jo A. ;
Shakhbazov, Konstantin ;
Visscher, Peter M. .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2013, 42 (05) :1497-1501
[6]   Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants [J].
Burgess, Stephen ;
Bowden, Jack ;
Fall, Tove ;
Ingelsson, Erik ;
Thompson, Simon G. .
EPIDEMIOLOGY, 2017, 28 (01) :30-42
[7]   Risk of Arterial Cardiovascular Diseases in Patients with Multiple Sclerosis: A Population-Based Cohort Study [J].
Christiansen, Christian Fynbo ;
Christensen, Steffen ;
Farkas, Dora Kormendine ;
Miret, Montserrat ;
Sorensen, Henrik Toft ;
Pedersen, Lars .
NEUROEPIDEMIOLOGY, 2010, 35 (04) :267-274
[8]   Mendelian randomization: genetic anchors for causal inference in epidemiological studies [J].
Davey Smith, George ;
Hemani, Gibran .
HUMAN MOLECULAR GENETICS, 2014, 23 :R89-R98
[9]   Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome [J].
Del Greco, Fabiola M. ;
Minelli, Cosetta ;
Sheehanc, Nuala A. ;
Thompsonc, John R. .
STATISTICS IN MEDICINE, 2015, 34 (21) :2926-2940
[10]   Multiple sclerosis - a review [J].
Dobson, R. ;
Giovannoni, G. .
EUROPEAN JOURNAL OF NEUROLOGY, 2019, 26 (01) :27-40