Decoding aortic dissection from potential drug targets to genetic risk factors: A Mendelian randomization study

Area of Science:

• Cardiovascular Genetics
• Pharmacogenomics
• Medical Research

Background:

• Aortic dissection (AD) is a life-threatening condition involving aortic wall damage.
• Current treatments for AD lack preventative medications.
• Identifying risk factors and therapeutic targets is crucial for AD management.

Purpose of the Study:

• To identify potential pharmacological targets for aortic dissection (AD).
• To evaluate the medicinal value and therapeutic potential of identified targets.
• To explore mediating factors in AD development.

Main Methods:

• Utilized Mendelian randomization (MR) with cis-expression quantitative trait loci (cis-eQTL) and genome-wide association analysis (GWAS) data.
• Performed colocalization analysis to identify shared genetic signals between drug targets and AD.
• Employed drug prediction and molecular docking to assess therapeutic potential.

Main Results:

• Identified 76 significantly associated genes through MR.
• Revealed five potential drug targets for AD via colocalization analysis.
• Confirmed drug-target associations using prediction and molecular docking; identified diastolic blood pressure, hip circumference, and ascending aorta diameter as potential mediators.

Conclusions:

• This research successfully identified five promising pharmacological targets for AD.
• Drug prediction and molecular docking validated the therapeutic potential of these targets.
• The findings are expected to enhance AD prediction and accelerate drug development efforts.