Causal relationship between immune cells and myocardial infarction: A Mendelian randomization study

Area of Science:

• Immunology
• Cardiovascular Disease Genetics
• Statistical Genetics

Background:

• Myocardial infarction (MI) is a leading global cause of death.
• The relationship between immune cells and MI is complex, with observational studies limited by confounding factors and reverse causality.
• Establishing a causal link between immune responses and MI is crucial for understanding disease mechanisms.

Purpose of the Study:

• To investigate the potential causal effect of genetically determined immune cell phenotypes on the risk of MI.
• To leverage large-scale genetic data to explore the etiological role of immune cells in MI.

Main Methods:

• A two-sample Mendelian randomization (MR) analysis was conducted using publicly available genome-wide association study data.
• Genetic variants associated with 731 immune cell signatures in Sardinians served as exposure instruments.
• Summary statistics for MI were used as the outcome, with inverse variance weighted, MR-egger, and simple median methods applied.

Main Results:

• Twenty-seven out of 731 immune cell phenotypes demonstrated a statistically significant causal association with MI.
• Fourteen immunophenotypes were inversely associated with MI risk, suggesting a protective role.
• Thirteen immunophenotypes were positively associated with MI, indicating an increased risk.

Conclusions:

• This genetic study provides robust evidence for a causal relationship between specific immune cell phenotypes and MI.
• Identified immune cell signatures may serve as novel biomarkers for MI risk prediction.
• These findings highlight potential new therapeutic targets for the prevention and treatment of MI.