Evaluating the cost-effectiveness of polygenic risk score-stratified screening for abdominal aortic aneurysm
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 (R<sup>2</sup>) 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.
Authors
- Angela Wood (ORCID: https://orcid.org/0000-0002-7937-304X)
- Emanuele Di Angelantonio (ORCID: https://orcid.org/0000-0001-8776-6719)
- John Danesh (ORCID: https://orcid.org/0000-0003-1158-6791)
- Michael Sweeting (ORCID: https://orcid.org/0000-0003-0980-8965)
- John D. O’Sullivan (ORCID: https://orcid.org/0000-0003-0422-8590)
- Lisa Pennells (ORCID: https://orcid.org/0000-0002-8594-3061)
- Michael Inouye (ORCID: https://orcid.org/0000-0001-9413-6520)
- Martin Kelemen (ORCID: https://orcid.org/0000-0002-4050-1817)
- Lois G. Kim (ORCID: https://orcid.org/0000-0002-4552-3820)
- Tarit Roychowdhury (ORCID: https://orcid.org/0000-0001-6515-5634)
- Simon James Harrison (ORCID: https://orcid.org/0000-0003-4555-6582)
Institutions
- Baker Heart and Diabetes Institute (AU)
- University of Leicester (GB)
- University of Cambridge (GB)
- British Heart Foundation (GB)
- Yale University (US)
- Cambridge University Health Partners (GB)
- Genomics (United Kingdom) (GB)
- Stanford University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-14
- DOI
- https://doi.org/10.1038/s41467-024-52452-w
- Citations
- 8
- Primary Topic
- Aortic aneurysm repair treatments
- Type
- article
- Field-Weighted Citation Impact
- 3.35
Funders
- Wellcome Trust
- Scottish Government
- UK Research and Innovation
- National Institute for Health and Care Research
- British Heart Foundation
- Department of Health and Social Care
- Public Health Agency
- Chief Scientist Office, Scottish Government Health and Social Care Directorate
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Economic and Social Research Council
- Health and Social Care Research and Development Division
- NIHR Cambridge Biomedical Research Centre