Non-alcoholic fatty liver disease and stroke: A Mendelian randomization study

Area of Science:

• Cardiovascular Epidemiology
• Hepatology
• Genetic Epidemiology

Background:

• Non-alcoholic fatty liver disease (NAFLD) association with stroke risk is inconsistent.
• Investigating a potential causal link between NAFLD and stroke is crucial for understanding disease mechanisms.

Purpose of the Study:

• To evaluate the causal relationship between NAFLD and stroke using Mendelian randomization.
• To examine the association of NAFLD with overall stroke, ischemic stroke, and its subtypes.

Main Methods:

• Utilized large-scale genome-wide association study data for NAFLD and stroke in European ancestry populations.
• Employed Mendelian randomization with inverse variant weighted methods to assess causal effects.
• Analyzed genetic associations for stroke, ischemic stroke, and subtypes: large artery atherosclerosis (LAA), small vessel occlusion (SVO), and cardioembolic stroke.

Main Results:

• NAFLD was not causally associated with overall stroke or ischemic stroke.
• A significant positive causal inference was observed between NAFLD and large artery atherosclerosis (LAA) stroke.
• NAFLD also showed a positive causal inference with small vessel occlusion (SVO) stroke, but not cardioembolic stroke.

Conclusions:

• The causal effect of NAFLD on ischemic stroke appears specific to large artery atherosclerosis (LAA) and small vessel occlusion (SVO) subtypes.
• These findings highlight specific stroke mechanisms potentially influenced by NAFLD.