Relationship between human serum metabolites and angina pectoris: a Mendelian randomization study

Area of Science:

• Metabolomics
• Cardiovascular Disease Genetics
• Biomarker Discovery

Background:

• Angina pectoris is a significant cardiovascular condition.
• Understanding the metabolic underpinnings of angina is crucial for developing effective diagnostic and therapeutic strategies.

Purpose of the Study:

• To investigate the causal relationships between human serum metabolites and angina pectoris.
• To identify specific metabolites and metabolic pathways associated with the risk of developing angina pectoris.

Main Methods:

• Utilized two-sample Mendelian randomization (MR) analysis on 486 serum metabolites.
• Employed inverse variance weighted, MR-Egger, and weighted median methods to assess associations.
• Conducted sensitivity analyses including leave-one-out and MR-Pleiotropy RESidual Sum and Outlier (RSO) tests.

Main Results:

• Identified 42 serum metabolites significantly associated with angina pectoris.
• These metabolites included amino acids, carbohydrates, lipids, and nucleotides.
• Pipecolate showed the highest risk, while glycine, serine, threonine, primary bile acid, and caffeine metabolism pathways were implicated.

Conclusions:

• Discovered 25 high-risk and 17 protective serum metabolites for angina pectoris.
• Established significant metabolic pathways linked to angina development.
• Highlighted pipecolate as a key metabolite positively correlated with angina risk, suggesting its potential as a serum biomarker.