Plasma proteins and coronary atherosclerosis: A Mendelian randomization study

Area of Science:

• Cardiovascular Research
• Genetics
• Biomarker Discovery

Background:

• Coronary atherosclerosis (AS) is a major cause of cardiovascular disease, posing a significant global health challenge.
• Current therapies for AS face limitations, highlighting the need for novel therapeutic targets.
• Identifying proteins with causal links to AS is crucial for advancing treatment strategies.

Purpose of the Study:

• To identify plasma proteins causally associated with coronary atherosclerosis (AS) using genetic variations.
• To leverage Mendelian randomization analysis for robust identification of potential therapeutic targets.
• To provide a foundation for developing new drugs and therapies for coronary AS.

Main Methods:

• Mendelian randomization analysis was employed using genome-wide association study data for 4907 plasma proteins.
• Inverse variance weighted (IVW) approach was the primary method, supplemented by weighted median, MR-Egger, and mode-based methods for validation.
• Sensitivity analyses, including leave-one-out, were performed to ensure result robustness and exclude biases.

Main Results:

• Twenty potential therapeutic targets were identified with a P-value < .05.
• Fibronectin 1 was highlighted as a key protein target through integrated bioinformatic analyses.
• The study established causal relationships between specific plasma proteins and coronary AS.

Conclusions:

• Fibronectin 1 represents a promising therapeutic target for coronary atherosclerosis.
• This research offers a novel genetic basis for future drug development in cardiovascular disease.
• The findings support the potential for targeted therapies to address limitations in current AS treatment.