scholarly journals A Mendelian randomization analysis of the relationship between cardioembolic risk factors and ischemic stroke

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danyang Tian ◽  
Linjing Zhang ◽  
Zhenhuang Zhuang ◽  
Tao Huang ◽  
Dongsheng Fan
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Mendelian Randomization ◽  
P Wave ◽  
Cardioembolic Stroke ◽  
Large Artery ◽  
Weighted Analysis ◽  
Inverse Variance ◽  
Weighted Median ◽  
Genetically Determined

AbstractObservational studies have shown that several risk factors are associated with cardioembolic stroke. However, whether such associations reflect causality remains unknown. We aimed to determine whether established and provisional cardioembolic risk factors are causally associated with cardioembolic stroke. Genetic instruments for atrial fibrillation (AF), myocardial infarction (MI), electrocardiogram (ECG) indices and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were obtained from large genetic consortiums. Summarized data of ischemic stroke and its subtypes were extracted from the MEGASTROKE consortium. Causal estimates were calculated by applying inverse-variance weighted analysis, weighted median analysis, simple median analysis and Mendelian randomization (MR)-Egger regression. Genetically predicted AF was significantly associated with higher odds of ischemic stroke (odds ratio (OR): 1.20, 95% confidence intervals (CI): 1.16–1.24, P = 6.53 × 10–30) and cardioembolic stroke (OR: 1.95, 95% CI: 1.85–2.06, P = 8.81 × 10–125). Suggestive associations were found between genetically determined resting heart rate and higher odds of ischemic stroke (OR: 1.01, 95% CI: 1.00–1.02, P = 0.005), large-artery atherosclerotic stroke (OR: 1.02, 95% CI: 1.00–1.04, P = 0.026) and cardioembolic stroke (OR: 1.02, 95% CI: 1.00–1.04, P = 0.028). There was no causal association of P‐wave terminal force in the precordial lead V1 (PTFVI), P-wave duration (PWD), NT-pro BNP or PR interval with ischemic stroke or any subtype.

Abstract P656: Cardioembolic Risk Factors and Ischemic Stroke a Mendelian Randomization Analysis

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Danyang Tian ◽  
Linjing Zhang ◽  
Zhenhuang Zhuang ◽  
Tao Huang ◽  
Dongsheng Fan
Keyword(s):  
Risk Factors ◽  
Heart Rate ◽  
Ischemic Stroke ◽  
P Wave ◽  
Cardioembolic Stroke ◽  
Large Artery ◽  
Inverse Variance ◽  
Pr Interval ◽  
Genetically Determined ◽  
Relationship Of

Background: Cardioembolic stroke accounts for a large proportion of ischemic stroke. Observational studies have shown that several risk factors are associated with cardioembolic stroke. However, whether such associations reflect causality remains unknown. Objectives: We aimed to determine whether established and provisional cardioembolic risk factors are causally associated cardioembolic stroke, and whether they have pathways of causal influence on other ischemic stroke subtypes. Methods: Genetic instruments for atrial fibrillation (AF), myocardial infarction (MI), some electrocardiogram (ECG) indices and NT-pro BNP were obtained from large genetic consortiums. Summarized data of ischemic stroke and its subtypes were extracted from the MEGASTROKE consortium. Causal estimates were calculated by applying inverse variance-weighted analysis and other methods. Results: Genetically predicted AF was significantly associated with higher odds of ischemic stroke (OR 1.20, 95% CI 1.16-1.24, P=6.53х10 -30 ) and cardioembolic stroke (OR 1.95, 95% CI 1.85-2.06, P=8.81х10 -125 ). Genetically predicted MI was significantly associated with higher odds of large artery stroke (OR 1.487, 95% CI 1.25-1.77, P=9.53х10 -6 ). Suggestive associations were found between genetically determined resting heart rate and higher odds of ischemic stroke (OR 1.01, 95% CI 1.00-1.02, P=0.005), large artery stroke (OR 1.02, 95% CI 1.00-1.04, P=0.026) and cardioembolic stroke (OR 1.02, 95% CI 1.00-1.04, P=0.028). There was no causal association of P-wave terminal force in the precordial lead V1 (PTFVI), P-wave duration (PWD), N-terminal-pro-brain Natriuretic Peptide (NT-pro BNP) or PR interval with ischemic stroke or any subtypes. Conclusion: Genetic predisposition to AF and heart rate are associated with cardioembolic stroke. No evidence of causality relationship of MI, PTFVI, PWD, NT-pro BNP and PR interval on cardioembolic stroke is found.

scholarly journals No Causal Effect of Telomere Length on Ischemic Stroke and Its Subtypes: A Mendelian Randomization Study

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 159 ◽  
Author(s):  
Weijie Cao ◽  
Xingang Li ◽  
Xiaoyu Zhang ◽  
Jie Zhang ◽  
Qi Sun ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Telomere Length ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Genome Wide Association Studies ◽  
Large Artery ◽  
Genome Wide ◽  
Inverse Variance ◽  
A Genome ◽  
Weighted Median

Background: Epidemiological studies observing inconsistent associations of telomere length (TL) with ischemic stroke (IS) are susceptible to bias according to reverse causation and residual confounding. We aimed to assess the causal association between TL, IS, and the subtypes of IS, including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES) by performing a series of two-sample Mendelian randomization (MR) approaches. Methods: Seven single nucleotide polymorphisms (SNPs) were involved as candidate instrumental variables (IVs), summarized from a genome-wide meta-analysis including 37,684 participants of European descent. We analyzed the largest ever genome-wide association studies of stroke in Europe from the MEGASTROKE collaboration with 40,585 stroke cases and 406,111 controls. The weighted median (WM), the penalized weighted median (PWM), the inverse variance weighted (IVW), the penalized inverse variance weighted (PIVW), the robust inverse variance weighted (RIVW), and the Mendelian randomization-Egger (MR-Egger) methods were conducted for the MR analysis to estimate a causal effect and detect the directional pleiotropy. Results: No significant association between genetically determined TL with overall IS, LAS, or CES were found (all p > 0.05). SVS was associated with TL by the RIVW method (odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.54–0.97, p = 0.028), after excluding rs9420907, rs10936599, and rs2736100. Conclusions: By a series of causal inference approaches using SNPs as IVs, no strong evidence to support the causal effect of shorter TL on IS and its subtypes were found.

Patient Demographics, Characteristics, and Intrahospital Mortality of Different Ischemic Stroke Subtypes in a Tertiary Hospital during Five-Year Period

2021 ◽  
Vol 6 (1) ◽  
pp. 6
Author(s):  
Sintija Strautmane ◽  
Kristaps Jurjāns ◽  
Estere Zeltiņa ◽  
Evija Miglāne ◽  
Andrejs Millers
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Reperfusion Therapy ◽  
Cardioembolic Stroke ◽  
Study Group ◽  
Large Artery ◽  
Patient Demographics ◽  
Stroke Subtypes ◽  
Female Predominance ◽  
Study Population

Background and Objectives. Ischemic stroke (IS) is one of the leading causes of disability, morbidity, and mortality worldwide. The goal of the study was to evaluate patient demographics, characteristics, and intrahospital mortality among different ischemic stroke subtypes. Materials and Methods. A retrospective observational non-randomized study was conducted, including only ischemic stroke patients, admitted to Pauls Stradins Clinical university hospital, Riga, Latvia, from January of 2016 until December 2020. Ischemic stroke subtypes were determined according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria as a stroke due to (1) large-artery atherosclerosis (atherothrombotic stroke (AS)), (2) cardioembolism (cardioembolic stroke (CS)), (3) small-vessel occlusion (lacunar stroke (LS)), (4) stroke of other determined etiology (other specified stroke (OSS)), and (5) stroke of undetermined etiology (undetermined stroke (US)). The data between different stroke subtypes were compared. Results. There was a slight female predominance among our study population, as 2673 (56.2%) patients were females. In our study group, the most common IS subtypes were cardioembolic stroke (CS), 2252 (47.4%), and atherothrombotic stroke (AS), 1304 (27.4%). CS patients were significantly more severely disabled on admission, 1828 (81.4%), and on discharge, 378 (16.8%), p < 0.05. Moreover, patients with CS demonstrated the highest rate of comorbidities and risk factors. This was also statistically significant, p < 0.05. Differences between the total patient count with no atrial fibrillation (AF), paroxysmal AF, permanent AF, and different IS subtypes among our study population demonstrated not only statistical significance but also a strong association, Cramer’s V = 0.53. The majority of patients in our study group were treated conservatively, 3389 (71.3%). Reperfusion therapy was significantly more often performed among CS patients, 770 (34.2%), p < 0.05. The overall intrahospital mortality among our study population was 570 (12.0%), with the highest intrahospital mortality rate noted among CS patients, 378 (66.3%), p < 0.05. No statistically significant difference was observed between acute myocardial infarction and adiposity, p > 0.05. Conclusions. In our study, CS and AS were the most common IS subtypes. CS patients were significantly older with slight female predominance. CS patients demonstrated the greatest disability, risk factors, comorbidities, reperfusion therapy, and intrahospital mortality.

Abstract T P153: Women and Men with Ischemic Stroke in SiGN Have Different Subtype Distributions and Risk Factors

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Kathryn M Rexrode ◽  
Braxton D Mitchell ◽  
Kathleen A Ryan ◽  
Steven J Kittner ◽  
Hakan Ay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Stroke Risk ◽  
Cardioembolic Stroke ◽  
Relative Distribution ◽  
Large Artery ◽  
Stroke Risk Factors ◽  
Stroke Subtypes ◽  
Small Artery Occlusion ◽  
Ischemic Stroke Risk

Introduction: The relative distribution of stroke risk factors, as well as ischemic stroke subtypes, in women compared with men is not well described. Hypothesis: We hypothesized that the distribution of ischemic stroke risk factors and subtypes would differ by sex, with a later onset in women and greater proportion of comorbidities. Methods: The NINDS Stroke Genetics Network (SiGN) consortium was established to evaluate genetic risk factors for ischemic stroke. A total of 23 separate studies performed Causative Classification of Stroke (CCS) typing using standardized criteria on ischemic stroke cases and contributed data on risk factors. We compared the distribution of ischemic stroke risk factors and CCS phenotypes between men and women with ischemic stroke. Results: Of the 16,228 ischemic strokes in SiGN, 8005 (49.3%) occurred in women. Median age at stroke was older in female than male stroke cases (73 vs. 66 years) (p=<0.0001). Among stroke cases, women were more likely than men cases to have hypertension or atrial fibrillation and less likely to have diabetes or coronary artery disease, or to smoke (p <0.003 for all). The distribution of stroke subtypes also differed by sex, with women less likely than men to have large artery infarction and small artery occlusion, and more likely to have cardioembolic stroke and undetermined stroke due to incomplete work-up (p values all <0.0001; see Table). Results were similar when the distribution of stroke subtypes was examined for those <70 years and ≥70 years, except for cardioembolic stroke remaining more common only among women ≥70. Conclusions: In this large group of carefully phenotyped ischemic strokes, the distribution of ischemic stroke subtypes and risk factor profiles differ significantly by sex. Evaluation of the causes of these differences may highlight areas for improved prevention and risk reduction in both genders.

scholarly journals Causal relationships between genetically determined metabolites and human intelligence: A Mendelian randomization study

2020 ◽  
Author(s):  
Jian Yang ◽  
Binbin Zhao ◽  
Li Qian ◽  
Fengjie Gao ◽  
Yanjuan Fan ◽  
...  
Keyword(s):  
Complex Traits ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Human Intelligence ◽  
Causal Relationships ◽  
Biological Mechanisms ◽  
Inverse Variance ◽  
Weighted Median ◽  
Genetic And Environmental Factors ◽  
Genetically Determined

Abstract Intelligence predicts important life and health outcomes, but the biological mechanisms underlying differences in intelligence are not yet understood. The use of genetically determined metabotypes (GDMs) to understand the role of genetic and environmental factors, and their interactions, in human complex traits has been recently proposed. However, this strategy has not been applied to human intelligence. Here we implemented a two-sample Mendelian randomization (MR) analysis using GDMs to assess the causal relationships between genetically determined metabolites and human intelligence. The standard inverse-variance weighted (IVW) method was used for the primary MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Using 25 genetic variants as instrumental variables (IVs), our study found that 5-oxoproline was associated with better performance in human intelligence tests (P IVW = 9 · 25×10 -5 ). The causal relationship was robust when sensitivity analyses were applied (P MR-Egger = 0 · 0001, P Weighted median = 6 · 29×10 -6 , P MR-PRESSO = 0 · 0007), and no evidence of horizontal pleiotropy was observed. Similarly, also dihomo-linoleate (20:2n6) and p-acetamidophenylglucuronide showed robust association with intelligence. Our study provides novel insight by integrating genomics and metabolomics to estimate causal effects of genetically determined metabolites on human intelligence, which help to understanding of the biological mechanisms related to human intelligence.

scholarly journals Causal relationships between genetically determined metabolites and human intelligence: a Mendelian randomization study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jian Yang ◽  
Binbin Zhao ◽  
Li Qian ◽  
Fengjie Gao ◽  
Yanjuan Fan ◽  
...  
Keyword(s):  
Complex Traits ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Human Intelligence ◽  
Causal Relationships ◽  
Biological Mechanisms ◽  
Inverse Variance ◽  
Weighted Median ◽  
Genetic And Environmental Factors ◽  
Genetically Determined

AbstractIntelligence predicts important life and health outcomes, but the biological mechanisms underlying differences in intelligence are not yet understood. The use of genetically determined metabotypes (GDMs) to understand the role of genetic and environmental factors, and their interactions, in human complex traits has been recently proposed. However, this strategy has not been applied to human intelligence. Here we implemented a two-sample Mendelian randomization (MR) analysis using GDMs to assess the causal relationships between genetically determined metabolites and human intelligence. The standard inverse-variance weighted (IVW) method was used for the primary MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Using 25 genetic variants as instrumental variables (IVs), our study found that 5-oxoproline was associated with better performance in human intelligence tests (PIVW = 9.25 × 10–5). The causal relationship was robust when sensitivity analyses were applied (PMR-Egger = 0.0001, PWeighted median = 6.29 × 10–6, PMR-PRESSO = 0.0007), and repeated analysis yielded consistent result (PIVW = 0.0087). Similarly, also dihomo-linoleate (20:2n6) and p-acetamidophenylglucuronide showed robust association with intelligence. Our study provides novel insight by integrating genomics and metabolomics to estimate causal effects of genetically determined metabolites on human intelligence, which help to understanding of the biological mechanisms related to human intelligence.

scholarly journals Carnitine and COVID-19 Susceptibility and Severity: A Mendelian Randomization Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Chunyu Li ◽  
Ruwei Ou ◽  
Qianqian Wei ◽  
Huifang Shang
Keyword(s):  
Causal Relationship ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Nucleotide Polymorphisms ◽  
Carnitine Level ◽  
Standard Deviation Increase ◽  
Inverse Variance ◽  
Weighted Median ◽  
Genetically Determined

Background: Carnitine, a potential substitute or supplementation for dexamethasone, might protect against COVID-19 based on its molecular functions. However, the correlation between carnitine and COVID-19 has not been explored yet, and whether there exists causation is unknown.Methods: A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship between carnitine level and COVID-19. Significant single nucleotide polymorphisms from genome-wide association study on carnitine (N = 7,824) were utilized as exposure instruments, and summary statistics of the susceptibility (N = 1,467,264), severity (N = 714,592) and hospitalization (N = 1,887,658) of COVID-19 were utilized as the outcome. The causal relationship was evaluated by multiplicative random effects inverse variance weighted (IVW) method, and further verified by another three MR methods including MR Egger, weighted median, and weighted mode, as well as extensive sensitivity analyses.Results: Genetically determined one standard deviation increase in carnitine amount was associated with lower susceptibility (OR: 0.38, 95% CI: 0.19–0.74, P: 4.77E−03) of COVID-19. Carnitine amount was also associated with lower severity and hospitalization of COVID-19 using another three MR methods, though the association was not significant using the IVW method but showed the same direction of effect. The results were robust under all sensitivity analyses.Conclusions: A genetic predisposition to high carnitine levels might reduce the susceptibility and severity of COVID-19. These results provide better understandings on the role of carnitine in the COVID-19 pathogenesis, and facilitate novel therapeutic targets for COVID-19 in future clinical trials.

scholarly journals Genetically Predicted Cardiac Troponin I Concentrations and Risk of Stroke and Atrial Fibrillation

2021 ◽  
Author(s):  
Dandan Liu ◽  
Yue Deng ◽  
Jiao Wang ◽  
Yanan Chen ◽  
Jian Yu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Mendelian Randomization ◽  
Cardiac Troponin I ◽  
Cardioembolic Stroke ◽  
Large Artery ◽  
Increased Risk

Abstract Background: Observational studies have shown that elevated circulating cardiac troponin I (cTnI) concentrations were associated with higher risk of stroke and atrial fibrillation, but the causality remains unclear. Therefore, we conducted a two-sample mendelian randomization study to evaluate the causal effects of cTnI concentrations on the risk of stroke subtypes and atrial fibrillation.Methods: The instrumental variables for circulating cTnI concentrations were selected from a genome-wide association study meta-analysis of 48,115 European individuals. Applying a 2-sample mendelian randomization approach, we examined the associations of circulating cTnI concentrations with stroke (40,585 cases and 406,111 controls), ischemic stroke (34,217 cases and 406,111 controls), ischemic stroke subtypes (cardioembolic, large artery, small vessel stroke), intracerebral hemorrhage (1,545 cases and 1,481 controls) and atrial fibrillation (60,620 cases and 970,216 controls). Results: Genetically predicted elevated circulating cTnI concentrations were associated with increased risk of cardioembolic stroke (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.20-2.68; P = 0.004). However, no significant association was observed for cTnI concentrations with large artery stroke, small vessel stroke, total stroke, ischemic stroke and intracerebral hemorrhage. Additionally, we also found that elevated cTnI concentrations were associated with higher risk of atrial fibrillation (OR, 1.30; 95% CI, 1.10-1.53; P = 0.003).Conclusions: This study provides evidence that genetically predicted circulating cTnI concentrations are causally associated with increased risk of cardioembolic stroke and atrial fibrillation.

scholarly journals Causal relationships between genetically determined metabolites and human intelligence: A Mendelian randomization study

2020 ◽  
Author(s):  
Jian Yang ◽  
Binbin Zhao ◽  
Li Qian ◽  
Fengjie Gao ◽  
Yanjuan Fan ◽  
...  
Keyword(s):  
Complex Traits ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Human Intelligence ◽  
Causal Relationships ◽  
Biological Mechanisms ◽  
Inverse Variance ◽  
Weighted Median ◽  
Genetic And Environmental Factors ◽  
Genetically Determined

Abstract Intelligence predicts important life and health outcomes, but the biological mechanisms underlying differences in intelligence are not yet understood. The use of genetically determined metabotypes (GDMs) to understand the role of genetic and environmental factors, and their interactions, in human complex traits has been recently proposed. However, this strategy has not been applied to human intelligence. Here we implemented a two-sample Mendelian randomization (MR) analysis using GDMs to assess the causal relationships between genetically determined metabolites and human intelligence. The standard inverse-variance weighted (IVW) method was used for the primary MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Using 25 genetic variants as instrumental variables (IVs), our study found that 5-oxoproline was associated with better performance in human intelligence tests (PIVW = 9·25 × 10− 5). The causal relationship was robust when sensitivity analyses were applied (PMR−Egger = 0·0001, PWeighted median = 6·29 × 10− 6, PMR−PRESSO = 0·0007), and no evidence of horizontal pleiotropy was observed. Similarly, also dihomo-linoleate (20:2n6) and p-acetamidophenylglucuronide showed robust association with intelligence. Our study provides novel insight by integrating genomics and metabolomics to estimate causal effects of genetically determined metabolites on human intelligence, which help to understanding of the biological mechanisms related to human intelligence.

scholarly journals Omega-6 fatty acids and the Risk of Cardiovascular Disease: Insights from a Systematic Review and Meta-Analysis of Randomized Controlled Trials and a Mendelian Randomization Study.

2021 ◽  
Author(s):  
Mohsen Mazidi ◽  
Niloofar Shekoohi ◽  
Niki Katsiki ◽  
Maciej Banach ◽  
the Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Sequential Analysis ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
Large Artery ◽  
Inverse Variance ◽  
Omega 6 ◽  
Adrenic Acid

IntroductionThe effects of omega-6 PUFAs on the CV risk factors are still controversial. Thus, we performed a systematic review and meta-analysis of RCTs as well as a Mendelian Randomization analysis to evaluate the links and possible causality between omega-6 PUFA, CVD and cardiometabolic risk factors.Material and methodsSelected databases were searched until September 2019 to identify prospective studies investigating the effects of omega-6 PUFAs supplementation on CVD events/mortality. Random-effects model meta-analysis was performed for quantitative data synthesis. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 20% reduction in outcomes after administration of omega-6 PUFAs. Inverse variance weighted method (IVW), weighted median-based method, MR-Egger and MR-PRESSO were applied for MR.ResultsThe pooled estimate risk ratio (RR) of omega-6 PUFAs supplementation was 0.94 for any CVD event (95%CI:0.77-1.15, I2=66.2%), 1.06 for CVD death (95%CI:0.73-1.55, I2=66.2%), 0.84 for coronary heart disease (CHD) events (95%CI:0.61-1.16, I2=79.4%), 0.87 for myocardial infarction (MI) (95%CI:0.74-1.01, I2=2.3%) and 1.36 for stroke (95%CI:0.45-4.07, I2=55.3%). In contrast, MR showed that individuals with higher serum adrenic acid (AA) levels had a greater risk for CHD events (IVW=Beta:0.526), MI (IVW=Beta:0.606) and large artery stroke (IVW=Beta:1.694), as well as increased levels of FBG (IVW=Beta:0.417), LDL-C (IVW=Beta:0.806,) HDL-C (IVW=Beta:0.820), and lower levels of triglycerides (TG) (IVW=Beta:-1.064) and total cholesterol (TC) (IVW=Beta:-1.064).ConclusionsOmega-6 PUFAs supplementation did not affect the risk for CVD morbidity and mortality. Additionally, in MR analysis we showed that higher AA levels might even significantly increase with the risk of CHD, MI and large artery stroke.

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