Predicting Thoracic Aortic Dissection in a Diverse Biobank Using a Polygenic Risk Score.

Area of Science:

• Genetics
• Cardiovascular Medicine
• Bioinformatics

Background:

• Thoracic aortic dissection (TAD) is a life-threatening condition often linked to aortic dilation.
• Current risk assessment relies heavily on aortic diameter, with limited clinical factors for individual risk stratification.

Purpose of the Study:

• To investigate the utility of common variant genetics in improving the identification of individuals at high risk for TAD.
• To develop a genetic risk score for predicting dissection independent of aortic diameter.

Main Methods:

• A genome-wide association study (GWAS)-by-subtraction approach was used to identify diameter-independent genetic factors for TAD.
• A polygenic risk score (PRS) was calculated and applied to participants in the Penn Medicine BioBank.
• Statistical analyses were performed using R version 4.3.2.

Main Results:

• Forty-three genetic risk loci associated with dissection were identified, forming the basis of a "Dissection-PRS".
• The Dissection-PRS was significantly associated with prevalent dissection in the BioBank cohort (OR: 2.13 per 1 SD increase).
• The PRS remained a robust predictor of dissection even after adjusting for aortic diameter and other clinical factors, significantly improving model discrimination (AUC increased from 0.676 to 0.723).

Conclusions:

• Common genetic variants, captured by a PRS, can effectively predict the risk of aortic dissection in a diverse population.
• The Dissection-PRS offers a valuable tool to enhance individual-level risk assessment for thoracic aortic dissection, complementing existing clinical measures.