Mendelian Randomization Study of Obesity and Cerebrovascular Disease.
Blood Glucose
/ genetics
Blood Pressure
/ genetics
Body Mass Index
Cerebral Hemorrhage
/ epidemiology
Cerebral Small Vessel Diseases
/ epidemiology
Cerebrovascular Disorders
/ epidemiology
Humans
Mendelian Randomization Analysis
Obesity
/ epidemiology
Stroke
/ epidemiology
Waist-Hip Ratio
White Matter
/ diagnostic imaging
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
01
07
2019
revised:
19
01
2020
accepted:
20
01
2020
pubmed:
25
1
2020
medline:
28
7
2020
entrez:
25
1
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31975536
doi: 10.1002/ana.25686
pmc: PMC7392199
mid: NIHMS1608309
doi:
Substances chimiques
Blood Glucose
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
516-524Subventions
Organisme : NIDDK NIH HHS
ID : K24 DK110550
Pays : United States
Organisme : American Heart Association-American Stroke Association
ID : 18POST34080063
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS103924
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS093870
Pays : United States
Organisme : NIH Clinical Center
ID : K23NS086873
Pays : International
Organisme : NIH Clinical Center
ID : R01NS093870
Pays : International
Organisme : NINDS NIH HHS
ID : K23 NS086873
Pays : United States
Informations de copyright
© 2020 American Neurological Association.
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