scholarly journals Genetic Liability to Sedentary Behavior in Relation to Stroke, Its Subtypes and Neurodegenerative Diseases: A Mendelian Randomization Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Fangkun Yang ◽  
Songzan Chen ◽  
Zihao Qu ◽  
Kai Wang ◽  
Xiaojie Xie ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Ischemic Stroke ◽  
Neurodegenerative Diseases ◽  
Cognitive Performance ◽  
Mendelian Randomization ◽  
Cerebrovascular Diseases ◽  
Causal Association ◽  
Sedentary Behaviors ◽  
Television Watching ◽  
Increased Risk

Objective: To investigate the causal association of domain-specific sedentary behaviors with cerebrovascular diseases and neurodegenerative diseases, and the potential mediators among these associations.Methods: Genetic instruments were identified for television watching, computer use and driving behavior from a genome-wide association study including 408,815 subjects. Mendelian randomization (MR) analysis was used to estimate the causal effect of sedentary behaviors on the cerebrovascular diseases and neurodegenerative diseases. Multivariable MR analysis was applied to adjust potential confounding factors, and mediation analysis was conducted to explore potential mediators.Results: Genetically predisposition to 1.5 h/day increase in leisure time watching television was associated with increased risk of all-cause stroke [odds ratio (OR) = 1.32, 95% confidence interval (CI) = 1.15–1.52, p-value for MR-Egger method (PEgger) = 0.11, I2 = 37%, Cochrane’s Q = 212, p-value for Cochran Q test (PQ) < 0.001], and ischemic stroke (OR = 1.28, 95%CI = 1.10–1.49, PEgger = 0.04, I2 = 35%, Cochrane’s Q = 206, PQ = 0.002). Interestingly, television watching may decrease the risk of Parkinson’s disease (OR = 0.65, 95%CI = 0.50–0.84, PEgger = 0.47, I2 = 19%, Cochrane’s Q = 157, PQ = 0.04). Television watching was a detrimental factor of cognitive performance (estimate = −0.46, 95%CI = −0.55 – −0.37, PEgger = 0.001, I2 = 85%, Cochrane’s Q = 862, PQ < 0.001). Sensitivity analyses using leave out method and MR-PRESSO method suggested weak evidence of pleiotropy.Conclusion: We provided genetic evidence for the causal association of television watching with increased risk of all-cause stroke and ischemic stroke, decreased risk of Parkinson’s disease, and worse cognitive performance. The results should be interpreted with caution considering the pleiotropy.

scholarly journals Genetic predisposition to television watching increases the risk of type 2 diabetes: a bidirectional and multivariable Mendelian randomization study

2020 ◽  
Author(s):  
Songzan Chen ◽  
Fangkun Yang ◽  
Tian Xu ◽  
Yao Wang ◽  
Kaijie Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Predisposition ◽  
Computer Use ◽  
Mendelian Randomization ◽  
Driving Behavior ◽  
Sensitivity Analyses ◽  
Sedentary Behaviors ◽  
Television Watching ◽  
Increased Risk

Abstract Background: Excessive sedentary behaviors have been reported to be associated with increased risk of type 2 diabetes, but whether this association is causal remains unclear. In current study, we aimed to investigate the causal association between domain-specific sedentary behaviors and the risk of type 2 diabetes using a two-sample Mendelian randomization (MR) study. Methods: We identified 165 single nucleotide polymorphisms as instrumental variables for television watching, 43 for computer use and 5 for driving behavior from a recently published genome-wide association study (n = 408,815). Genetic association estimates for type 2 diabetes were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (74,124 cases and 824,006 controls). The inverse variance-weighted method was used to estimate the effect of genetically predicted sedentary behaviors on the risk of type 2 diabetes. Reverse MR analysis was performed to investigate the reverse causation. The weighted median method, MR-Egger method, and MR Pleiotropy Residual Sum and Outlier method were employed in the sensitivity analyses. In addition, multivariable MR analysis and mediation analysis were conducted to explore the potential mechanistic elements.Results: Genetic predisposition to excessive television watching was associated with increased risk of type 2 diabetes. The OR (95% CI) per 1.5h (1 standard deviation) increment in television watching time was 1.82 (1.61, 2.07) for type 2 diabetes. This association was substantially attenuated after adjustment for anthropometric traits (adjusting BMI: OR = 1.35, 95% CI = 1.17 – 1.57, P = 4.1 × 10-5; adjusting WHR: OR = 1.26, 95% CI = 1.09 – 1.45, P = 1.4 × 10-3) and educational attainment (OR = 1.49, 95% CI = 1.16 – 1.91, P = 1.7 × 10-3). There was limited evidence of associations of computer use and driving behavior with the risk of type 2 diabetes. Conclusions: Our study clarifies the causal effect of excessive television watching on the increased risk of type 2 diabetes from a genetic perspective, which may be partly mediated via anthropometric and educational traits. Television watching may serve as a behavioral target to prevent incident diabetes.

EXPRESS: Effect of genetic liability to visceral adiposity on stroke and its subtypes: a Mendelian randomization study

2021 ◽  
pp. 174749302110062
Author(s):  
Bin Yan ◽  
Jian Yang ◽  
Li Qian ◽  
Fengjie Gao ◽  
Ling Bai ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Ischemic Stroke ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Visceral Adiposity ◽  
Large Artery ◽  
Nucleotide Polymorphisms ◽  
Genetic Liability ◽  
A Genome ◽  
Increased Risk

Background: Observational studies have found an association between visceral adiposity and stroke. Aims: The purpose of this study was to investigate the role and genetic effect of visceral adipose tissue (VAT) accumulation on stroke and its subtypes. Methods: In this two-sample Mendelian randomization (MR) study, genetic variants (221 single nucleotide polymorphisms; P<5×10-8) using as instrumental variables for MR analysis was obtained from a genome-wide association study (GWAS) of VAT. The outcome datasets for stroke and its subtypes were obtained from the MEGASTROKE consortium (up to 67,162 cases and 453,702 controls). MR standard analysis (inverse variance weighted method) was conducted to investigate the effect of genetic liability to visceral adiposity on stroke and its subtypes. Sensitivity analysis (MR-Egger, weighted median, MR-PRESSO) were also utilized to assess horizontal pleiotropy and remove outliers. Multi-variable MR analysis was employed to adjust potential confounders. Results: In the standard MR analysis, genetically determined visceral adiposity (per 1 SD) was significantly associated with a higher risk of stroke (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.21-1.41, P=1.48×10-11), ischemic stroke (OR 1.30; 95% CI 1.20-1.41, P=4.01×10-10), and large artery stroke (OR 1.49; 95% CI 1.22-1.83, P=1.16×10-4). The significant association was also found in sensitivity analysis and multi-variable MR analysis. Conclusions: Genetic liability to visceral adiposity was significantly associated with an increased risk of stroke, ischemic stroke, and large artery stroke. The effect of genetic susceptibility to visceral adiposity on the stroke warrants further investigation.

scholarly journals Occupational Exposures and Neurodegenerative Diseases—A Systematic Literature Review and Meta-Analyses

2019 ◽  
Vol 16 (3) ◽  
pp. 337 ◽  
Author(s):  
Lars-Gunnar Gunnarsson ◽  
Lennart Bodin
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Occupational Exposure ◽  
Neurodegenerative Diseases ◽  
Meta Analysis ◽  
Occupational Exposures ◽  
Increased Risk ◽  
Meta Analyses

Objectives: To carry out an integrated and stratified meta-analysis on occupational exposure to electromagnetic fields (EMFs), metals and pesticides and its effects on amyotrophic lateral sclerosis (ALS) and Parkinson’s and Alzheimer’s disease, and investigate the possibility of publication bias. Methods: In the current study, we updated our recently published meta-analyses on occupational exposures in relation to ALS, Alzheimer’s and Parkinson’s disease. Based on 66 original publications of good scientific epidemiological standard, according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines, we analysed subgroups by carrying out stratified meta-analyses on publication year, statistical precision of the relative risk (RR) estimates, inspection of the funnel plots and test of bias. Results: Based on 19 studies the weighted RR for occupational exposure to EMFs was 1.26 (95% confidence interval (CI) 1.07–1.50) for ALS, 1.33 (95% CI 1.07–1.64) for Alzheimer’s disease and 1.02 (95% CI 0.83–1.26) for Parkinson’s disease. Thirty-one studies concerned occupational exposure to pesticides and the weighted RR was 1.35 (95% CI 1.02–1.79) for ALS, 1.50 (95% CI 0.98–2.29) for Alzheimer’s disease and 1.66 (95% CI 1.42–1.94) for Parkinson’s disease. Finally, 14 studies concerned occupational exposure to metals and only exposure to lead (five studies) involved an elevated risk for ALS or Parkinson’s disease and the weighted RR was 1.57 (95% CI 1.11–2.20). The weighted RR for all the non-lead exposures was 0.97 (95% CI 0.88–1.06). Conclusions: Exposure to pesticides increased the risk of getting the mentioned neurodegenerative diseases by at least 50%. Exposure to lead was only studied for ALS and Parkinson’s disease and involved 50% increased risk. Occupational exposure to EMFs seemed to involve some 10% increase in risk for ALS and Alzheimer’s disease only.

scholarly journals Assessment of Atrial Conduction Times in Patients with Newly Diagnosed Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Yiğit Çanga ◽  
Ayşe Emre ◽  
Gülbün Asuman Yüksel ◽  
Mehmet Baran Karataş ◽  
Nizamettin Selçuk Yelgeç ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ischemic Stroke ◽  
Electromechanical Coupling ◽  
P Wave ◽  
Volume Index ◽  
Newly Diagnosed ◽  
Increased Risk ◽  
Atrial Conduction Times

Background. An increased risk of ischemic stroke has been reported in patients with Parkinson’s disease (PD). Atrial fibrillation (AF) is strongly associated with ischemic stroke. Prolonged atrial electromechanical delay (EMD) is an independent predictor for the development of AF. Aims. The aim of the present study was to evaluate the atrial conduction parameters in patients with PD and to assess their relation with the severity of PD. Study design. We prospectively enrolled 51 consecutive patients with newly diagnosed PD and 31 age- and sex-matched non-PD subjects. Methods. To assess atrial electromechanical coupling (PA), the time intervals from the onset of p wave on ECG to the late diastolic wave at the septal (PAs) and lateral (PAl) mitral annulus and lateral tricuspid annulus (PAt) were measured on Tissue Doppler Echocardiography (TDE). The difference between PAs-PAl, PAs-PAt, and PAl-PAt were defined as left intra-atrial, right intra-atrial, and interatrial EMD, respectively. P-wave dispersion (PWD) was calculated from the 12-lead ECG. Results. PWD, PAs, PAl, and PAt durations were significantly prolonged in the PD group (all p<0.001). Interatrial, right, and left intra-atrial EMD were also significantly longer in PD patients (p<0.001, p<0.001 and p=0.002, resp.). There were significant positive correlations between disease severity (UPDRS score) and PWD (r=0.34, p=0.041), left intra-atrial (r=0.39, p=0.005), and interatrial EMD (r=0.35, p=0.012). By multivariate analysis, PWD (OR: 1.13, 95% CI: 1.02–1.25; p=0.017), LA volume index (OR: 1.19, 95% CI: 1.02–1.37; p=0.021), left intra-atrial (OR: 1.12, 95% CI: 1.01–1.24; p=0.041), and interatrial EMD (OR: 1.08, 95% CI: 1.01–1.16; p=0.026) were found as independent predictors of PD. Conclusion. Atrial conduction times were longer and correlated with the severity of disease in PD patients. Prolonged inter- and intra-atrial-EMD intervals were also found as independent correlates of PD. These findings may suggest an increased predisposition to atrial fibrillation in PD.

scholarly journals Mendelian randomization to evaluate the effect of plasma vitamin C levels on the risk of Alzheimer’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Haijie Liu ◽  
Yan Zhang ◽  
Yang Hu ◽  
Haihua Zhang ◽  
Tao Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vitamin C ◽  
Cognitive Performance ◽  
Large Scale ◽  
Mendelian Randomization ◽  
Plasma Vitamin ◽  
Causal Association ◽  
Uk Biobank ◽  
Gwas Dataset

Abstract Objective Until now, observational studies have explored the impact of vitamin C intake on Alzheimer’s disease (AD) risk, however, reported ambiguous findings. To develop effective therapies or prevention, the causal link between vitamin C levels and AD should be established. Methods Here, we selected 11 plasma vitamin C genetic variants from a large-scale plasma vitamin C GWAS dataset (N = 52,018) as the potential instrumental variables. We extracted their corresponding summary statistics from large-scale IGAP clinically diagnosed AD GWAS dataset (N = 63,926) and UK Biobank AD proxy phenotype GWAS dataset (N = 314,278), as well as two UK Biobank subgroups including the maternal AD group (27,696 cases of maternal AD and 260,980 controls) and paternal AD group (14,338 cases of paternal AD and 245,941 controls). We then performed a Mendelian randomization (MR) study to evaluate the causal association between plasma vitamin C levels and the risk of AD and AD proxy phenotype. Meanwhile, we further verified these findings using a large-scale cognitive performance GWAS dataset (N = 257,841). Results In IGAP, we found no significant causal association between plasma vitamin C levels and the risk of AD. In UK Biobank, we found that per 1 SD increase in plasma vitamin C levels (about 20.2 μmol/l) was significantly associated with the reduced risk of AD proxy phenotype (OR = 0.93, 95% CI 0.88–0.98, P = 7.00E−03). A subgroup MR analysis in UK Biobank indicated that per 1 SD increase in plasma vitamin C levels could significantly reduce the risk of AD proxy phenotype in the maternal AD group (OR = 0.89, 95% CI 0.84–0.94, P = 7.29E−05), but not in the paternal AD group (OR = 1.02, 95% CI 0.92–1.12, P = 7.59E−01). The leave-one-out permutation further showed that the SLC23A1 rs33972313 variant largely changed the precision of the overall MR estimates in all these four GWAS datasets. Meanwhile, we did not observe any significant causal effect of plasma vitamin C levels on the cognitive performance. Conclusion We demonstrated that there may be no causal association between plasma vitamin C levels and the risk of AD in people of European descent. The insistent findings in clinically diagnosed AD and AD proxy phenotype may be caused by the phenotypic heterogeneity.

scholarly journals Association of 25 hydroxyvitamin D concentration with risk of COVID-19: a Mendelian randomization study

2020 ◽  
Author(s):  
Di Liu ◽  
Qiuyue Tian ◽  
Jie Zhang ◽  
Haifeng Hou ◽  
Wei Wang ◽  
...  
Keyword(s):  
Causal Relationship ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25Ohd Concentration ◽  
25 Hydroxyvitamin D

Background In observational studies, 25 hydroxyvitamin D (25OHD) concentration has been associated with an increased risk of Coronavirus disease 2019 (COVID-19). However, it remains unclear whether this association is causal. Methods We performed a two-sample Mendelian randomization (MR) to explore the causal relationship between 25OHD concentration and COVID-19, using summary data from the genome-wide association studies (GWASs) and using 25OHD concentration-related SNPs as instrumental variables (IVs). Results MR analysis did not show any evidence of a causal association of 25OHD concentration with COVID-19 susceptibility and severity (odds ratio [OR]=1.136, 95% confidence interval [CI] 0.988-1.306, P=0.074; OR=0.889, 95% CI 0.549-1.439, P=0.632). Sensitivity analyses using different instruments and statistical models yielded similar findings, suggesting the robustness of the causal association. No obvious pleiotropy bias and heterogeneity were observed. Conclusion The MR analysis showed that there might be no linear causal relationship of 25OHD concentration with COVID-19 susceptibility and severity.

scholarly journals HIV Associated Risk Factors for Ischemic Stroke and Future Perspectives

2020 ◽  
Vol 21 (15) ◽  
pp. 5306
Author(s):  
Saifudeen Ismael ◽  
Mohammad Moshahid Khan ◽  
Prashant Kumar ◽  
Sunitha Kodidela ◽  
Golnoush Mirzahosseini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Hiv Infection ◽  
Opportunistic Infections ◽  
Experimental Studies ◽  
Chronic Administration ◽  
Cerebrovascular Diseases ◽  
Vascular Abnormalities ◽  
Increased Risk ◽  
The Impact

Although retroviral therapy (ART) has changed the HIV infection from a fatal event to a chronic disease, treated HIV patients demonstrate high prevalence of HIV associated comorbidities including cardio/cerebrovascular diseases. The incidence of stroke in HIV infected subjects is three times higher than that of uninfected controls. Several clinical and postmortem studies have documented the higher incidence of ischemic stroke in HIV infected patients. The etiology of stroke in HIV infected patients remains unknown; however, several factors such as coagulopathies, opportunistic infections, vascular abnormalities, atherosclerosis and diabetes can contribute to the pathogenesis of stroke. In addition, chronic administration of ART contributes to the increased risk of stroke in HIV infected patients. Concurrently, experimental studies in murine model of ischemic stroke demonstrated that HIV infection worsens stroke outcome, increases blood brain barrier permeability and increases neuroinflammation. Additionally, residual HIV viral proteins, such as Trans-Activator of Transcription, glycoprotein 120 and Negative regulatory factor, contribute to the pathogenesis. This review presents comprehensive information detailing the risk factors contributing to ischemic stroke in HIV infected patients. It also outlines experimental evidence demonstrating the impact of HIV infection on stroke outcomes, in addition to possible novel therapeutic approaches to improve these outcomes.

scholarly journals Sleep Duration and Stroke

Stroke ◽  
2020 ◽  
Vol 51 (11) ◽  
pp. 3279-3285
Author(s):  
Olga E. Titova ◽  
Karl Michaëlsson ◽  
Susanna C. Larsson
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Prospective Study ◽  
Sleep Duration ◽  
Mendelian Randomization ◽  
Short Sleep ◽  
Mendelian Randomization Analysis ◽  
Increased Risk ◽  
Long Sleep ◽  
Randomization Analysis

Background and Purpose: Studies of sleep duration in relation to specific types of stroke are scarce. Moreover, the results are inconclusive and causality remains unclear. Our objective was to investigate whether sleep duration is associated with risk of stroke and its types using observational and Mendelian randomization designs. Methods: The prospective study included 79 881 women and men (45–79 years of age) who were followed up for incident stroke or death over a mean follow-up of 14.6 years (1 164 646 person-years) through linkage to Swedish Registers. For the Mendelian randomization study, single-nucleotide polymorphisms associated with sleep duration were identified from a genome-wide association study. Summarized data for genetic associations with stroke were obtained from publicly available data of the MEGASTROKE and the International Stroke Genetics Consortia. Results: Compared with normal sleep duration, long sleep (≥9 hours per day) was associated with increased risk of total and ischemic stroke (hazard ratios [95% CI], 1.12 [1.03–1.22] and 1.14 [1.03–1.24], respectively), whereas short sleep (<7 h/d) was linked to higher risk of intracerebral hemorrhage (hazard ratio [95% CI], 1.21 [1.03–1.41]). The 2-sample Mendelian randomization analysis supported no causal association of short or long sleep duration with ischemic stroke as a whole. Conclusions: In a prospective study, long sleep duration was associated with increased risk of total and ischemic stroke, whereas short sleep was linked to increased risk of intracerebral hemorrhage. However, the Mendelian randomization analysis did not show a significant detrimental effect of short or long sleep duration on the risk of total stroke or stroke types.

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