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

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

M Kelemen  1   2 , J Danesh  1   2 , E Di Angelantonio  1   2 , M Inouye  1   2   3 , J O'Sullivan  4 , L Pennells  1   2 , T Roychowdhury  5 , M J Sweeting  6 , A M Wood  1   2 , S Harrison  7 , L G Kim  8   9
Affiliations

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

M Kelemen et al. Nat Commun. .

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.

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Conflict of interest statement

J.D. serves on scientific advisory boards for AstraZeneca, Novartis, and UK Biobank, and has received multiple grants from academic, charitable and industry sources outside of the submitted work. M.I. is a trustee of the Public Health Genomics (PHG) Foundation, a member of the Scientific Advisory Board of Open Targets, and has research collaborations with AstraZeneca, Nightingale Health and Pfizer which are unrelated to this study. M.J.S. reports full-time employment with AstraZeneca and AstraZeneca stock ownership. S.H. is an employee at Genomics PLC. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Observed non-parametric cumulative incidence curves for recorded AAA in the UKB test set.
The CIF is shown separately for women (left) and men (right). PRS groups correspond to tertiles of PRS risk. Shaded areas represent 95% confidence intervals for the cumulative incidence function. AAA abdominal aortic aneurysm, UKB UK Biobank, PRS polygenic risk score.
Fig. 2
Fig. 2. Incremental net benefit compared to no invitation, by age at invitation and baseline prevalence at age 60 in men.
INB is evaluated at a willingness-to-pay of £30,000 per QALY, based on 1 M hypothetical individuals in the DES. Points plotted are point estimates. Shaded areas represent 95% uncertainty intervals derived from 100 bootstrap PSA samples. PRS/smoking sub-group prevalences estimated from UKB test set as CIF x inflation factor; indicated on the x-axis. INB incremental net benefit, QALY quality-adjusted life-year, DES discrete event simulation, PSA probabilistic sensitivity analysis, PRS polygenic risk score, UKB UK Biobank, CIF cumulative incidence function, AAA abdominal aortic aneurysm.
Fig. 3
Fig. 3. Incremental net benefit compared to no invitation, by age at invitation and baseline prevalence at age 65 in women.
INB is evaluated at a willingness-to-pay of £30,000 per QALY, based on 1 M hypothetical individuals in the DES. Points plotted are point estimates. Shaded areas represent 95% uncertainty intervals derived from 100 bootstrap PSA samples. PRS/smoking sub-group prevalences estimated from UKB test set as CIF x inflation factor; indicated on the x-axis. INB incremental net benefit, QALY quality-adjusted life-year; DES discrete event simulation, PSA probabilistic sensitivity analysis, PRS polygenic risk score, UKB UK Biobank, CIF cumulative incidence function, AAA abdominal aortic aneurysm.
See this image and copyright information in PMC

References

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