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.

Kelemen et al. find that leveraging related traits improves polygenic score performance for abdominal aortic aneurysm. Health-economic modelling suggests that combining smoking and genetic risk information may improve cost-effectiveness of screening.

Details

Title
Evaluating the cost-effectiveness of polygenic risk score-stratified screening for abdominal aortic aneurysm
Author
Kelemen, M. 1 ; Danesh, J. 1 ; Di Angelantonio, E. 1 ; Inouye, M. 2   VIAFID ORCID Logo  ; O’Sullivan, J. 3 ; Pennells, L. 1   VIAFID ORCID Logo  ; Roychowdhury, T. 4 ; Sweeting, M. J. 5 ; Wood, A. M. 1   VIAFID ORCID Logo  ; Harrison, S. 6 ; Kim, L. G. 1   VIAFID ORCID Logo 

1  University of Cambridge, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); University of Cambridge, Victor Phillip Dahdaleh Heart and Lung Research Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934) 
2  University of Cambridge, British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); University of Cambridge, Victor Phillip Dahdaleh Heart and Lung Research Institute, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000 0001 2188 5934); Baker Heart & Diabetes Institute, Melbourne, Australia (GRID:grid.1051.5) (ISNI:0000 0000 9760 5620) 
3  Stanford University, Division of Cardiology, Department of Medicine, Stanford, USA (GRID:grid.168010.e) (ISNI:0000 0004 1936 8956) 
4  Yale School of Medicine, Department of Genetics, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710) 
5  University of Leicester, Department of Population Health Sciences, Leicester, UK (GRID:grid.9918.9) (ISNI:0000 0004 1936 8411) 
6  Genomics PLC, Oxford, UK (GRID:grid.510940.9) 
Pages
8063
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-024-52452-w
ProQuest document ID
3104620840
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.