Causal relationship between C-reactive protein and ischemic stroke caused by atherosclerosis: A Mendelian...

Area of Science:

• Cardiovascular Epidemiology
• Genetic Epidemiology
• Biomarkers in Stroke

Background:

• C-reactive protein (CRP) is a marker of inflammation.
• Inflammation plays a role in atherosclerosis.
• The causal link between CRP and ischemic stroke due to large artery atherosclerosis (LAA) requires further investigation.

Purpose of the Study:

• To investigate the potential causal association between C-reactive protein (CRP) and large artery atherosclerosis (LAA) ischemic stroke.
• To utilize Mendelian Randomization (MR) to assess this relationship.

Main Methods:

• Employed five Mendelian Randomization (MR) methods for two-sample analyses.
• Utilized aggregated summary statistics from a large genome-wide association study (GWAS) meta-analysis for CRP exposure (n=343,524).
• Analyzed stroke data, including LAA stroke, as the outcome (cases=40,585, controls=406,111).

Main Results:

• Inverse Variance Weighting (IVW) and Weighted Median (WM) methods indicated a significant causal relationship between CRP and LAA stroke.
• Weighted Mode analysis also supported a significant causal association.
• MR-Egger regression and Simple Mode did not find a significant causal link, with low horizontal pleiotropy.

Conclusions:

• Mendelian Randomization analysis provides evidence suggesting a potential causal relationship between elevated C-reactive protein (CRP) and an increased risk of LAA stroke.
• These findings highlight CRP as a potential therapeutic target for preventing LAA stroke.