scholarly journals Modifiable lifestyle factors and risk of stroke: a Mendelian randomization analysis

2020 ◽  
Author(s):  
Eric L Harshfield ◽  
Marios K Georgakis ◽  
Rainer Malik ◽  
Martin Dichgans ◽  
Hugh S Markus
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Educational Attainment ◽  
Ischaemic Stroke ◽  
Genetic Predisposition ◽  
Stroke Risk ◽  
Mendelian Randomization ◽  
Lifestyle Factors ◽  
Large Artery ◽  
Modifiable Lifestyle Factors

ABSTRACTAimsAssessing whether modifiable risk factors are causally associated with reduced stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data. Leveraging large-scale genetic data in a technique known as Mendelian randomisation, we aimed to determine whether modifiable lifestyle factors including educational attainment, smoking, and body mass index are causal risk factors for ischaemic stroke and its different subtypes and haemorrhagic stroke.Methods and ResultsWe performed two-sample and multivariable Mendelian randomization to assess the causal effect of twelve lifestyle factors on risk of stroke and whether these effects are independent. We found genetic predisposition to increased number of years of education to be inversely associated with ischaemic, large-artery, and small-vessel stroke, as well as with intracerebral haemorrhage. Genetic predisposition to ever smoking regularly, higher body mass index (BMI), and higher waist-hip ratio are also associated with ischaemic and large-artery stroke. Additionally, we found that the effects of education, BMI, and smoking on ischaemic stroke to be independent of each other.ConclusionGenetic predisposition to higher educational attainment can reduce the risk of ischaemic, large-artery, and small-vessel stroke, while genetic predisposition to smoking and higher anthropometry measures can increase the risk of these stroke subtypes. This suggests that lifestyle modification addressing these risk factors will reduce stroke risk.

scholarly journals Modifiable Lifestyle Factors and Risk of Stroke

Stroke ◽  
2021 ◽  
Author(s):  
Eric L. Harshfield ◽  
Marios K. Georgakis ◽  
Rainer Malik ◽  
Martin Dichgans ◽  
Hugh S. Markus
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Ischemic Stroke ◽  
Body Mass ◽  
Stroke Risk ◽  
Causal Effect ◽  
Lifestyle Factors ◽  
Small Vessel ◽  
Large Artery ◽  
Modifiable Lifestyle Factors

Background and Purpose: Assessing whether modifiable risk factors are causally associated with stroke risk is important in planning public health measures, but determining causality can be difficult in epidemiological data. We evaluated whether modifiable lifestyle factors including educational attainment, smoking, and body mass index are causal risk factors for ischemic stroke and its subtypes and hemorrhagic stroke. Methods: We performed 2-sample and multivariable Mendelian randomization to assess the causal effect of 12 lifestyle factors on risk of stroke and whether these effects are independent. Results: Genetically predicted years of education was inversely associated with ischemic, large artery, and small vessel stroke, and intracerebral hemorrhage. Genetically predicted smoking, body mass index, and waist-hip ratio were associated with ischemic and large artery stroke. The effects of education, body mass index, and smoking on ischemic stroke were independent. Conclusions: Our findings support the hypothesis that reduced education and increased smoking and obesity increase risk of ischemic, large artery, and small vessel stroke, suggesting that lifestyle modifications addressing these risk factors will reduce stroke risk.

scholarly journals Selection into shift work is influenced by educational attainment and body mass index: A Mendelian randomization study

2020 ◽  
Author(s):  
Iyas Daghlas ◽  
Rebecca C. Richmond ◽  
Jacqueline M. Lane ◽  
Hassan S. Dashti ◽  
Hanna M. Ollila ◽  
...  
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Educational Attainment ◽  
Body Mass ◽  
Shift Work ◽  
Cardiometabolic Risk ◽  
Mendelian Randomization ◽  
Cardiometabolic Risk Factors ◽  
Cardiometabolic Disease ◽  
Sleep Timing

AbstractBackgroundShift work is associated with increased cardiometabolic disease risk, but whether this association is influenced by cardiometabolic risk factors driving selection into shift work is currently unclear. We addressed this question using Mendelian randomization (MR) in the UK Biobank.MethodsWe created genetic risk scores (GRS) associating with nine cardiometabolic risk factors (including education, body mass index [BMI], smoking, and alcohol consumption), and tested associations of each GRS with self-reported current frequency of shift work and night shift work amongst employed UKB participants of European ancestry (n=190,573). We used summary-level MR sensitivity analyses and multivariable MR to probe robustness of the identified effects, and tested whether effects were mediated through sleep timing preference.ResultsGenetically instrumented lower educational attainment and higher body mass index increased odds of reporting frequent shift work (odds ratio [OR] per 3.6 years [1-SD] decrease in educational attainment=2.40, 95% confidence interval [CI]=2.22-2.59, p=4.84 × 10−20; OR per 4.7kg/m2 [1-SD] increase in BMI=1.30, 95%CI=1.14-1.47, p=5.85 × 10−05). Results were unchanged in sensitivity analyses allowing for different assumptions regarding horizontal pleiotropy, and the effects of education and BMI were independent in multivariable MR. No causal effects were evident for the remaining factors, nor for any exposures on selection out of shift work. Sleep timing preference did not mediate any causal effects.ConclusionsEducational attainment and BMI may influence selection into shift work, which may have implications for epidemiologic associations of shift work with cardiometabolic disease.Key messagesAlthough it has been hypothesized that cardiometabolic risk factors and diseases may influence selection into shift work, little evidence for such an effect is currently available.Using Mendelian randomization, we assessed whether cardiometabolic risk factors and diseases influenced selection into or out of shift work in the UK Biobank.Our results were consistent with a causal effect of both higher BMI and lower educational attainment on selection into current shift work, with stronger effects seen for shift work that is more frequent and includes more night shifts.Using multivariable Mendelian randomization, we found that effects of higher BMI and lower education were independent. Sleep timing preference had a null effect on shift work selection and therefore did not mediate these effects.Selection through education and BMI may bias the relationship of shift work with cardiometabolic disease. Social mechanisms underlying these effects warrant further investigation.

scholarly journals The impact of education inequality on rheumatoid arthritis risk is mediated by smoking and body mass index: mendelian randomization study

2021 ◽  
Author(s):  
Sizheng Steven Zhao ◽  
Michael V Holmes ◽  
Jie Zheng ◽  
Eleanor Sanderson ◽  
Alice R Carter
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Educational Attainment ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Total Effect ◽  
Smoking Exposure ◽  
Higher Educational ◽  
Higher Educational Attainment ◽  
The Impact

Objective. To estimate the causal relationship between educational attainment - as a proxy for socioeconomic inequality - and risk of RA and quantify the roles of cigarette smoking and body mass index (BMI) as potential mediators. Methods. Using the largest genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) study of genetically predicted educational attainment (instrumented using 1265 variants from GWAS of 766,345 individuals) and RA (14,361 cases, 43,923 controls). We used two-step MR to quantify the proportion of education's effect on RA mediated by smoking exposure (as a composite index capturing duration, heaviness and cessation, using 124 variants from 462,690 individuals) and BMI (517 variants, 681,275 individuals), and multivariable MR to estimate proportion mediated by both factors combined. Results. Each standard deviation (SD) increase in educational attainment (4.2 years of schooling) was protective of RA (OR 0.37; 95%CI 0.31, 0.44). Higher educational attainment was also protective for smoking exposure (b= -0.25 SD; 95%CI -0.26, -0.23) and BMI (b= -0.27 SD (~1.3kg/m2); 95%CI -0.31, -0.24). Smoking mediated 24% (95%CI 13%, 35%) and BMI 17% (95%CI 11%, 23%) of the total effect of education on RA. Combined, the two risk factors explained 47% (95%CI 11%, 82%) of the total effect. Conclusion. Higher educational attainment has a protective effect on RA risk. Interventions to reduce smoking and excess adiposity at a population level may reduce this risk, but a large proportion of education's effect on RA remains unexplained. Further research into other risk factors that act as potentially modifiable mediators are required.

scholarly journals Cardiac Risk Factors for Stroke: A Comprehensive Mendelian Randomization Study

Stroke ◽  
2021 ◽  
Author(s):  
Simon Frerich ◽  
Rainer Malik ◽  
Marios K. Georgakis ◽  
Moritz F. Sinner ◽  
Steven J. Kittner ◽  
...  
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Genetic Predisposition ◽  
Mendelian Randomization ◽  
Genetic Data ◽  
Cardiac Risk ◽  
Large Artery ◽  
Artery Disease

Background and Purpose: Observational studies suggest an association of stroke with cardiac traits beyond atrial fibrillation, the leading source of cardioembolism. However, controversy remains regarding a causal role of these traits in stroke pathogenesis. Here, we leveraged genetic data to systematically assess associations between cardiac traits and stroke risk using a Mendelian Randomization framework. Methods: We studied 66 cardiac traits including cardiovascular diseases, magnetic resonance imaging–derived cardiac imaging, echocardiographic imaging, and electrocardiographic measures, as well as blood biomarkers in a 2-sample Mendelian Randomization approach. Genetic predisposition to each trait was explored for associations with risk of stroke and stroke subtypes in data from the MEGASTROKE consortium (40 585 cases/406 111 controls). Using multivariable Mendelian Randomization, we adjusted for potential pleiotropic or mediating effects relating to atrial fibrillation, coronary artery disease, and systolic blood pressure. Results: As expected, we observed strong independent associations between genetic predisposition to atrial fibrillation and cardioembolic stroke and between genetic predisposition to coronary artery disease as a proxy for atherosclerosis and large-artery stroke. Our data-driven analyses further indicated associations of genetic predisposition to both heart failure and lower resting heart rate with stroke. However, these associations were explained by atrial fibrillation, coronary artery disease, and systolic blood pressure in multivariable analyses. Genetically predicted P-wave terminal force in V1, an electrocardiographic marker for atrial cardiopathy, was inversely associated with large-artery stroke. Conclusions: Available genetic data do not support substantial effects of cardiac traits on the risk of stroke beyond known clinical risk factors. Our findings highlight the need to carefully control for confounding and other potential biases in studies examining candidate cardiac risk factors for stroke.

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 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 A bi-directional Mendelian randomization study of glycemic and anthropometric traits and Parkinson’s disease

2020 ◽  
Author(s):  
Sandeep Grover ◽  
Ricarda Graf ◽  
Alastair Noyce ◽  
Manu Sharma ◽  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Genetic Predisposition ◽  
Mendelian Randomization ◽  
Fat Distribution ◽  
European Population ◽  
P Value ◽  
Log Odds ◽  
Effect Of Pd

AbstractImportanceImpaired glucose and obesity are known characteristics of patients with PD, although it is unclear whether the dysfunction precedes or results from the neurodegeneration.ObjectiveTo assess whether glycemic traits and anthropometric traits can influence the risk of PD in 33,674 cases and 449,056 healthy controls using Mendelian randomization (MR) framework.Design, setting, and participantsWe investigated causality with a two-sample bidirectional MR approach in the European population. We used the inverse variance-weighted (IVW), weighted median (WME), and weighted mode (MBE) methods to compute effect estimates with summary statistics from available meta-analyses of genome-wide association studies (GWAS) on glycemic and anthropometric traits that used discovery cohorts. We conducted sensitivity analyses with prioritized genetic instruments that used different study designs including employment of different study cohorts and body mass index (BMI) adjusted exposures, and exclusion of overlapping samples between risk factors and outcome datasets, and potential pleiotropic genetic instruments.Main outcome and measuresPD, glycemic and anthropometric traitsResultsWe observed a risky effect of PD on fasting glucose (FG) (IVW: β = 0.0188 per log-odds of PD; 95% CI 0.0062–0.0313, p-value = 0.0055). We further observed a protective effect of PD on type 2 diabetes (T2D) (WME: OR = 0.946 per log-odds of PD; 95% CI 0.929–0.983, p-value = 0.0051). A direct causal role of waist-hip ratio (WHR) was also observed in PD (IVW OR = 0.735; 95% CI = 0.622-0.868 per 1-SD of WHR, p = 0.0003). However, the association was lost after WHR was adjusted for body mass index (BMI) (IVW OR = 0.889; 95% CI = 0.779-1.037 per 1-SD of WHR adjusted for BMI, p = 0.1429) indicating that the observed association is mediated via BMI The associations were further retained after the exclusion of overlapping UK Biobank (UKB) samples in the PD dataset.Conclusions and relevanceOur results showed that PD patients are glucose tolerant with protection against T2D. Furthermore, central obesity may be protective against PD development, independent of glucose levels. The implication of different indices of glycemic control and body fat distribution on the PD symptomatology deserves further investigation.Key pointsQuestionAre glucose and obesity associated with Parkinson’s disease?FindingsUsing bi-directional Mendelian randomization (MR) approach, and using Parkinson disease (PD) as an exposure, our study found that a 1-log odds increase in genetic predisposition to PD was associated with 0.0188 mmol/l increase in fasting glucose concentration. The genetic predisposition to PD was also associated with a 5.4% lower risk of type-2 diabetes (T2D). We found that a 1-SD increase in waist-hip ratio (WHR) was associated with a 26.5% lower risk of PD in the European population, likely to be mediated via body mass index.MeaningA strong genetic predisposition towards glucose tolerance was observed in PD patients. and PD patients are protective against T2D. Further, an increase in WHR lowers the risk of PD. Our study thereby suggests potential roles of body fat distribution and glycemic traits on PD symptomatology.

scholarly journals Subtypes, Risk Factors and Site of Stenosis of Ischaemic Stroke in a University Hospital in Bangladesh

2021 ◽  
pp. 11
Author(s):  
Mohammad Shahidullah ◽  
Nahid Sultana ◽  
Subash Kanti Dey ◽  
Anis Ahmed
Keyword(s):  
Risk Factors ◽  
Magnetic Resonance ◽  
Ischaemic Stroke ◽  
Cross Sectional Study ◽  
University Hospital ◽  
Large Artery ◽  
Stroke Patients ◽  
Vessel Occlusion ◽  
Cross Sectional ◽  
Common Cause

Stoke is the second most common cause of death and the most common cause of adult disability. To plan an efficient evaluation and treatment of an individual patient with ischaemic stroke, the clinician should be familiar with the subtyping of ischaemic stroke patients and the risk factors analysis of different aetiology. Eight hundred seventy-seven (877) patients have been selected for this cross-sectional study conducted in a university hospital of Bangladesh from 2014 to 2018, to whom brain imaging [Computed Tomography (CT)/ Magnetic Resonance Imaging (MRI)], vascular imaging [Magnetic Resonance Angiogram (MRA), Digital Subtraction Angiogram (DSA)], ECG and echocardiography have been done. We did subtyping according to TOAST criteria. The mean age of patients was 60.5 ± 11 years. Most patients (29.33%) belonged to the age group 51 – 60, where 70.47% of subjects were male and 29.53% were female. In this study, 43.87% of patients were in the large artery atherosclerosis group, 23.83.% in the small vessel occlusion group, 8.46% in the cardiac embolism group, 19.30% in the undetermined aetiology group and 4.54% in other determined aetiology. Among risk factors hypertension, diabetes mellitus, dyslipidaemia was present in 58.15%, 38.42%, and 38.88% of patients, respectively. In ischaemic stroke patients, large artery atherosclerosis was the most common subtype and hypertension was significant in this group. Extracranial stenosis was more common in ischaemic stroke.

scholarly journals Diabetes Mellitus, Glycemic Traits, and Cerebrovascular Disease: A Mendelian Randomization Study

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011555
Author(s):  
Marios K. Georgakis ◽  
Eric L. Harshfield ◽  
Rainer Malik ◽  
Nora Franceschini ◽  
Claudia Langenberg ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Ischemic Stroke ◽  
White Matter ◽  
Genetic Predisposition ◽  
Mendelian Randomization ◽  
Small Vessel ◽  
Large Artery ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Hba1c Levels

Objective:We employed Mendelian randomization (MR) to explore the effects of genetic predisposition to type 2 diabetes (T2D), hyperglycemia, insulin resistance, and β-cell dysfunction on risk of stroke subtypes and related cerebrovascular phenotypes.Methods:We selected instruments for genetic predisposition to T2D (74,124 cases, 824,006 controls), HbA1c levels (n=421,923), fasting glucose levels (n=133,010), insulin resistance (n=108,557), and β-cell dysfunction (n=16,378) based on published genome-wide association studies. Applying two-sample MR, we examined associations with ischemic stroke (60,341 cases, 454,450 controls), intracerebral hemorrhage (1,545 cases, 1,481 controls), and ischemic stroke subtypes (large artery, cardioembolic, small vessel stroke), as well as with related phenotypes (carotid atherosclerosis, imaging markers of cerebral white matter integrity, and brain atrophy).Results:Genetic predisposition to T2D and higher HbA1c levels were associated with higher risk of any ischemic stroke, large artery stroke, and small vessel stroke. Similar associations were also noted for carotid atherosclerotic plaque, fractional anisotropy, a white matter disease marker, and markers of brain atrophy. We further found associations of genetic predisposition to insulin resistance with large artery and small vessel stroke, whereas predisposition to β-cell dysfunction was associated with small vessel stroke, intracerebral hemorrhage, lower grey matter volume, and total brain volume.Conclusions:This study supports causal effects of T2D and hyperglycemia on large artery and small vessel stroke. We show associations of genetically predicted insulin resistance and β-cell dysfunction with large artery and small vessel stroke that might have implications for anti-diabetic treatments targeting these mechanisms.Classification of Evidence:This study provides Class II evidence that genetic predisposition to T2D and higher HbA1c levels are associated with a higher risk of large artery and small vessel ischemic stroke.

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