Relationships between obesity and functional outcome after ischemic stroke: a Mendelian randomization study
Jieyi Lu1,2, Siqi Gong1,2, Juehua Zhu3
1Department of Neurology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, 215006, China.
Summary
Genetically predicted higher waist-to-hip ratio (WHR) is linked to worse functional outcomes after ischemic stroke. However, body mass index (BMI) showed no significant association, suggesting targeted obesity interventions may improve stroke recovery.
Area of Science:
- Genetics
- Neurology
- Public Health
Background:
- Obesity's impact on ischemic stroke outcomes is debated, with some studies suggesting a protective effect (obesity paradox).
- Previous research indicates obesity may worsen functional outcomes post-stroke.
- Genetic predisposition to obesity requires further investigation regarding stroke recovery.
Purpose of the Study:
- To investigate the association between genetically predicted obesity and functional outcomes following ischemic stroke using Mendelian randomization (MR).
- To differentiate the effects of body mass index (BMI) and waist-to-hip ratio (WHR) on post-stroke functional recovery.
Main Methods:
- Utilized large-scale genetic data from UK Biobank and GIANT consortium for BMI and WHR instrumental variables.
- Obtained functional outcome data from the Genetics of Ischemic Stroke Functional Outcome network.
- Employed inverse-variance weighted (IVW) analysis as the primary method, with sensitivity analyses using alternative MR methods and heterogeneity assessments (I², Q statistics).
Main Results:
- Univariable MR showed a significant association between genetic liability to WHR and worse functional outcome (mRS 3) after ischemic stroke (OR=1.47 [1.07, 2.02], P=0.016).
- Genetic liability to BMI was not significantly associated with post-stroke functional outcome (P>0.05).
- Multivariable MR analysis, adjusting for BMI, attenuated the association between WHR and functional outcome (OR=1.26 [0.76, 1.67], P=0.56).
Conclusions:
- Genetic predisposition to a higher WHR, but not BMI, is correlated with unfavorable functional outcomes after ischemic stroke.
- Findings suggest that interventions targeting central obesity (reflected by WHR) may be beneficial for improving stroke recovery.
- Further research into the specific mechanisms linking WHR to stroke outcomes is warranted.
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