RESEARCHERS have demonstrated that incorporating a polygenic score with clinical features significantly improves the estimation of ascending aortic diameter and the prediction of adverse thoracic aortic events. The research focused on enhancing traditional clinical models by including a polygenic score derived from 1.1 million genetic variants, termed the AORTA Gene score.
The AORTA Gene model is composed of a polygenic score derived from a genome-wide association study of 39,524 participants, and clinical data from 4896 participants. Researchers evaluated the performance of this enhanced model across multiple large biobanks, including the UK Biobank, Mass General Brigham (MGB) Biobank, the Framingham Heart Study (FHS), and the All of Us research program. The researchers found that the AORTA Gene model explained a larger proportion of variance in thoracic aortic diameter than clinical factors alone, ranging from 34.9% to 41.8% across the different cohorts, compared to 28.9% to 33.0% with clinical factors alone.
Moreover, the AORTA Gene model significantly outperformed traditional models in identifying individuals with an ascending aortic diameter of 4 cm or greater, a critical threshold for predicting adverse events. For example, in the UK Biobank, the area under the receiver operating characteristic curve (AUC) was 0.836 for the AORTA Gene model compared to 0.776 for the clinical-only model, with similar improvements observed in other cohorts.
Importantly, the study also showed that the AORTA Gene model was more informative for predicting adverse thoracic aortic events in both the UK Biobank and All of Us participants, indicating its potential utility in clinical practice.
In conclusion, this study suggests that integrating polygenic risk scores with clinical data provides a more accurate estimation of aortic diameter and a better prediction of thoracic aortic events, which could lead to improved screening and prevention strategies for at-risk individuals.
Katrina Thornber, EMJ
Reference
Pirruccello JP et al. The AORTA Gene score for detection and risk stratification of ascending aortic dilation. Eur Heart J. 2024;DOI:10.1093/eurheartj/ehae474.
