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

Nature Communications (Sep 2024)

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

Affiliations

M. Kelemen: British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
J. Danesh: British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
E. Di Angelantonio: British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
M. Inouye: British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
J. O’Sullivan: Division of Cardiology, Department of Medicine, Stanford University
L. Pennells: British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
T. Roychowdhury: Department of Genetics, Yale School of Medicine
M. J. Sweeting: Department of Population Health Sciences, University of Leicester
A. M. Wood: British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
S. Harrison: Genomics PLC
L. G. Kim: British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge

DOI: https://doi.org/10.1038/s41467-024-52452-w
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 10

Abstract

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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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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