Exploring Stroke Risk through Mendelian Randomization: A Comprehensive Study Integrating Genetics and Metabolic...

Area of Science:

• Genetics
• Cardiovascular Medicine
• Neurology

Background:

• Cardiometabolic conditions are significant stroke risk factors.
• Korean medicine utilizes constitutional types for disease treatment.
• Constitutional types exhibit variations in cardiometabolic disease prevalence.

Purpose of the Study:

• To investigate the causal effects of genetic characteristics on stroke risk.
• To analyze these effects based on Korean constitutional types.
• To compare Mendelian randomization estimates across different constitutional groups.

Main Methods:

• Applied Mendelian randomization (MR) to assess genetic associations with stroke.
• Utilized data from large-scale genetic consortia (MEGASTROKE, ISGC, UKbiobank, BBJ).
• Employed single nucleotide polymorphisms (SNPs) as instrumental variables for MR analysis.

Main Results:

• TE constitutional subtypes, prone to metabolic disease, showed a significant increase in cardioembolic stroke (CES) risk (beta = 4.190, p = 0.035).
• SE constitutional subtypes demonstrated a significant decrease in CES risk (beta = -9.336, p = 3.87 × 10^-5).
• Clinical analysis indicated significant differences in diabetes and dyslipidemia among subtypes.

Conclusions:

• Constitutional type is a critical factor in genetic predisposition to stroke subtypes.
• Personalized medicine approaches are essential for accurate stroke risk assessment.
• Findings support tailoring stroke risk evaluation based on individual constitutional profiles.