Causal associations between CD40/CD40L and aortic diseases: A mendelian randomization study.

Area of Science:

• Genetics and Cardiovascular Disease Epidemiology
• Immunology and Aortic Pathologies

Background:

• Previous studies suggested associations between CD40/CD40L and aortic diseases (AD/AA).
• Causality of these associations remained unestablished prior to this research.

Purpose of the Study:

• To assess the causal inference between CD40/CD40L and aortic dissection (AD) and aortic aneurysm (AA).
• To utilize Mendelian randomization (MR) for robust causal effect estimation.

Main Methods:

• A two-sample Mendelian randomization (MR) study design was employed.
• Instrumental variables for CD40 and CD40L were derived from a large European ancestry protein quantitative trait loci dataset.
• Genome-wide association study summary statistics for AD and AA (including TAA and AAA subtypes) were utilized.

Main Results:

• Genetic evidence indicated that CD40 levels are inversely associated with the risk of AD (OR: 0.777) and AA (OR: 0.905).
• These associations were consistent across thoracic AA (TAA) and abdominal AA (AAA) subtypes.
• CD40L showed a trend towards increased risk for AD and AA, but did not reach statistical significance.

Conclusions:

• This MR study provides strong evidence for a causal relationship between CD40 and reduced risks of both AD and AA.
• The findings highlight CD40 as a potential therapeutic target for preventing aortic diseases.