Mendelian Randomization Study of Obesity and Cerebrovascular Disease

Autor: Martin Dichgans, Jordi Merino, Rainer Malik, Jose C. Florez, Catherine Sudlow, Bailey Montgomery, Jonathan Rosand, Sandro Marini, Dipender Gill, Christopher D. Anderson
Rok vydání: 2020
Předmět:
Blood Glucose
0301 basic medicine
genetics [Blood Pressure]
genetics [Cerebrovascular Disorders]
INTRACEREBRAL HEMORRHAGE
Blood Pressure
epidemiology [Cerebral Hemorrhage]
Body Mass Index
genetics [Obesity]
0302 clinical medicine
GENETIC-VARIANTS
Stroke
ASSOCIATIONS
RISK
White Matter
PREVALENCE
ISCHEMIC-STROKE
FAT MASS
Neurology
ABDOMINAL OBESITY
genetics [Stroke]
Cardiology
ADIPOSITY
Life Sciences & Biomedicine
epidemiology [Cerebral Small Vessel Diseases]
epidemiology [Stroke]
medicine.medical_specialty
genetics [Cerebral Hemorrhage]
Clinical Neurology
International Stroke Genetics Consortium
Article
diagnostic imaging [White Matter]
03 medical and health sciences
Internal medicine
Mendelian randomization
medicine
Genetic predisposition
Humans
Obesity
ddc:610
METAANALYSIS
Cerebral Hemorrhage
Intracerebral hemorrhage
Science & Technology
Neurology & Neurosurgery
epidemiology [Obesity]
Waist-Hip Ratio
business.industry
genetics [Blood Glucose]
Neurosciences
nutritional and metabolic diseases
1103 Clinical Sciences
Mendelian Randomization Analysis
medicine.disease
Confidence interval
Cerebrovascular Disorders
epidemiology [Cerebrovascular Disorders]
030104 developmental biology
Blood pressure
Cerebral Small Vessel Diseases
genetics [Cerebral Small Vessel Diseases]
Neurosciences & Neurology
Neurology (clinical)
1109 Neurosciences
business
Body mass index
030217 neurology & neurosurgery
Zdroj: Annals of neurology 87(4), 516-524 (2020). doi:10.1002/ana.25686
Marini, S, Merino, J, Montgomery, B E, Malik, R, Sudlow, C L, Dichgans, M, Florez, J C, Rosand, J, Gill, D & Anderson, C D 2020, ' Mendelian randomization study of obesity and cerebrovascular disease ', Annals of Neurology . https://doi.org/10.1002/ana.25686
Ann Neurol
ISSN: 1531-8249
0364-5134
DOI: 10.1002/ana.25686
Popis: Objective To systematically investigate causal relationships between obesity and cerebrovascular disease and the extent to which hypertension and hyperglycemia mediate the effect of obesity on cerebrovascular disease. Methods We used summary statistics from genome-wide association studies for body mass index (BMI), waist-to-hip ratio (WHR), and multiple cerebrovascular disease phenotypes. We explored causal associations with 2-sample Mendelian randomization (MR) accounting for genetic covariation between BMI and WHR, and we assessed what proportion of the association between obesity and cerebrovascular disease was mediated by systolic blood pressure (SBP) and blood glucose levels, respectively. Results Genetic predisposition to higher BMI did not increase the risk of cerebrovascular disease. In contrast, for each 10% increase in WHR there was a 75% increase (95% confidence interval [CI] = 44-113%) in risk for large artery ischemic stroke, a 57% (95% CI = 29-91%) increase in risk for small vessel ischemic stroke, a 197% increase (95% CI = 59-457%) in risk of intracerebral hemorrhage, and an increase in white matter hyperintensity volume (β = 0.11, 95% CI = 0.01-0.21). These WHR associations persisted after adjusting for genetic determinants of BMI. Approximately one-tenth of the observed effect of WHR was mediated by SBP for ischemic stroke (proportion mediated: 12%, 95% CI = 4-20%), but no evidence of mediation was found for average blood glucose. Interpretation Abdominal adiposity may trigger causal pathological processes, partially independent from blood pressure and totally independent from glucose levels, that lead to cerebrovascular disease. Potential targets of these pathological processes could represent novel therapeutic opportunities for stroke. ANN NEUROL 2020;87:516-524.
Databáze: OpenAIRE
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