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

Aims

The aortic dissection (AD) is defined as the destruction of the tunica media and separation of the aortic wall, which can be fatal. To date, there is no clinical medication that has been developed to effectively prevent the progression of AD. Therefore, it is imperative to identify risk factors associated with AD and to discover potential therapeutic targets.

Methods

To identify therapeutic targets for AD, we used cis-expression quantitative trait loci (cis-eQTL) data from the eQTLgen Consortium and genome-wide association analysis (GWAS) data from the Finngen Consortium for Mendelian randomization (MR). Colocalization analysis screened drug targets with shared SNPs in the disease. Drug prediction and molecular docking verified the targets' medicinal value. Finally, mediation analysis was performed to explore how drug targets might influence AD development.

Results

Using MR, we identified 76 genes exhibiting significant associations. Subsequent colocalization analysis revealed five drug targets sharing genetic signals with AD. Drug prediction analyses were conducted, and molecular docking demonstrated a robust association between the predicted drugs and the implicated genes. Furthermore, our findings suggest that diastolic blood pressure, hip circumference and ascending aorta diameter may serve as potential mediating factors in the development of AD.

Conclusion

This study identified five potential pharmacological targets for AD. Additionally, drug prediction and molecular docking were employed to assess the therapeutic potential of these targets. The findings of this research are anticipated to offer valuable screening indicators for AD prediction and facilitate advancements in AD drug development.