Evaluating the cost-effectiveness of polygenic risk score-stratified screening for abdominal aortic aneurysm

M Kelemen; J Danesh; E Di Angelantonio; M Inouye; J O'Sullivan; L Pennells; T Roychowdhury; M J Sweeting; A M Wood; S Harrison; L G Kim

doi:10.1038/s41467-024-52452-w

Evaluating the cost-effectiveness of polygenic risk score-stratified screening for abdominal aortic aneurysm

Nat Commun. 2024 Sep 14;15(1):8063. doi: 10.1038/s41467-024-52452-w.

Authors

M Kelemen^{1

2}, J Danesh^{1

2}, E Di Angelantonio^{1

2}, M Inouye^{1

2

3}, J O'Sullivan⁴, L Pennells^{1

2}, T Roychowdhury⁵, M J Sweeting⁶, A M Wood^{1

2}, S Harrison⁷, L G Kim^{8

9}

Affiliations

¹ British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
² Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.
³ Baker Heart & Diabetes Institute, Melbourne, Australia.
⁴ Division of Cardiology, Department of Medicine, Stanford University, Stanford, CA, USA.
⁵ Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
⁶ Department of Population Health Sciences, University of Leicester, Leicester, UK.
⁷ Genomics PLC, Oxford, UK.
⁸ British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [email protected].
⁹ Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK. [email protected].

Abstract

As the heritability of abdominal aortic aneurysm (AAA) is high and AAA partially shares genetic architecture with other cardiovascular diseases, genetic information could help inform AAA screening strategies. Exploiting pleiotropy and meta-analysing summary data from large studies, we construct a polygenic risk score (PRS) for AAA. Leveraging related traits improves PRS performance (R²) by 22.7%, relative to using AAA alone. Compared with the low PRS tertile, intermediate and high tertiles have hazard ratios for AAA of 2.13 (95%CI 1.61, 2.82) and 3.70 (95%CI 2.86, 4.80) respectively, adjusted for clinical risk factors. Using simulation modelling, we compare PRS- and smoking-stratified screening with inviting men at age 65 and not inviting women (current UK strategy). In a futuristic scenario where genomic information is available, our modelling suggests inviting male current smokers with high PRS earlier than 65 and screening female smokers with high/intermediate PRS at 65 and 70 respectively, may improve cost-effectiveness.

MeSH terms

Aged
Aortic Aneurysm, Abdominal* / diagnosis
Aortic Aneurysm, Abdominal* / genetics
Cost-Benefit Analysis*
Female
Genetic Predisposition to Disease*
Genetic Risk Score
Genetic Testing / economics
Genetic Testing / methods
Genome-Wide Association Study
Humans
Male
Mass Screening / economics
Mass Screening / methods
Middle Aged
Multifactorial Inheritance* / genetics
Risk Assessment
Risk Factors
Smoking

Grants and funding

RG/18/13/33946/British Heart Foundation (BHF)