| Title: | Polygenic risk score informed clinical model for improving abdominal aortic aneurysm screening |
| Journal: | Annals of Vascular Surgery |
| Published: | 25 Jul 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39067852/ |
| DOI: | https://doi.org/10.1016/j.avsg.2024.06.036 |
Publication 12775
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Abstract
INTRODUCTION: Abdominal aortic aneurysm (AAA) is a complex disease with environmental and genetic risk factors. Polygenic risk scores (PRS) based on disease-specific risk-associated single nucleotide variants (SNVs) have demonstrated effectiveness in stratifying individual-level disease risk for cardiovascular diseases. This prospective cohort study assessed associations of PRS of AAA (PRSAAA) with risk of incident AAA, analyzed the effectiveness of a combined clinical-genetic risk model, and explored the clinical utility of the model in identifying high-risk individuals for AAA screening.</p>
METHODS: PRSAAA was calculated using 911,440 SNVs and PRSCAD was calculated using 2,324,683 SNVs derived from mixed ancestry genome wide association studies. The UK Biobank was used as the study cohort. All individuals with complete genetic data available and no diagnosis of AAA at time of recruitment were included in the analysis and followed prospectively to assess for incident AAA. A PRS informed clinical model, Prob-AAA, was developed using clinically significant variables and PRSAAA.</p>
RESULTS: 481,105 individuals were included in the analysis with 2,668 incident AAA cases. Incident AAA increased from 0.30% to 0.93% between the lowest and highest decile of PRSAAA; similarly, severe AAA, requiring surgery and/or presenting with rupture, increased from 23% to 39% of incident AAA cases across deciles. PRSAAA was a predictor of incident AAA diagnosis (HR 2.06 [1.70 - 2.48]) independent of other clinical risk factors including male sex, older age, and smoking history. Prob-AAA was an independent predictor of incident AAA (HR 1.92 [1.69 - 2.20]), and identified 9.6% of cases of incident AAA compared to only 4.2% by PRSAAA. Current screening guidelines captured 5.7% of the overall cohort, with an incident AAA rate of approximately 3.2%. Amongst males not included by current guidelines, Prob-AAA identified an additional cohort, approximately 2% of the overall cohort, with a similar rate of incident AAA.</p>
CONCLUSIONS: Prob-AAA, a PRS informed clinical model for AAA, improved upon the predictive power of current, clinical risk factor informed, screening guidelines for AAA.</p>
7 Authors
- David Jiang
- Zhuqing Shi
- Jun Wei
- Huy Tran
- S Lilly Zheng
- Jianfeng Xu
- Cheong J Lee
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