Journal Article

DZNE-2020-01222

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Mendelian Randomization Study of Obesity and Cerebrovascular Disease.

Marini, S. (Corresponding author) ; Merino, J. ; Montgomery, B. E. ; Malik, R. ; Sudlow, C. L. ; Dichgans, M.DZNE* ; Florez, J. C. ; Rosand, J. ; Gill, D. ; Anderson, C. D.

2020
Wiley-Blackwell Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/ana.25686

Abstract: 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.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.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.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.

Keyword(s): Blood Glucose: genetics (MeSH) ; Blood Pressure: genetics (MeSH) ; Body Mass Index (MeSH) ; Cerebral Hemorrhage: epidemiology (MeSH) ; Cerebral Hemorrhage: genetics (MeSH) ; Cerebral Small Vessel Diseases: epidemiology (MeSH) ; Cerebral Small Vessel Diseases: genetics (MeSH) ; Cerebrovascular Disorders: epidemiology (MeSH) ; Cerebrovascular Disorders: genetics (MeSH) ; Humans (MeSH) ; Mendelian Randomization Analysis (MeSH) ; Obesity: epidemiology (MeSH) ; Obesity: genetics (MeSH) ; Stroke: epidemiology (MeSH) ; Stroke: genetics (MeSH) ; Waist-Hip Ratio (MeSH) ; White Matter: diagnostic imaging (MeSH) ; Blood Glucose

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Web of Science Core Collection

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