September 14, 2024Nature Communications11 citationsOpen Access
Evaluating the cost-effectiveness of polygenic risk score-stratified screening for abdominal aortic aneurysm
Key Result
A high polygenic risk score was associated with a 3.70-fold increased hazard of incident abdominal aortic aneurysm compared to a low score, supporting its potential use in stratified screening.
Study Design
Type
Cohort (n=91,731)
Structured PICO
Does PRS- and smoking-stratified screening improve cost-effectiveness for abdominal aortic aneurysm detection compared to current age- and sex-based screening strategies?
P
Population
91,731 individuals of European ancestry from the UK Biobank, free of prevalent abdominal aortic aneurysm at baseline, followed for a median of 12.0 years.
E
Exposure
Polygenic risk score (PRS)- and smoking-stratified screening for abdominal aortic aneurysm (e.g., inviting male current smokers with high PRS at age 60, and female smokers with high/intermediate PRS at 65 and 70).
C
Comparator
Current UK strategy (inviting men at age 65 and not inviting women) or no screening.
O
Outcome
Incident abdominal aortic aneurysm (AAA) and incremental net monetary benefit (INB) at a willingness-to-pay of £30,000 per QALY.hard clinical
A polygenic risk score for abdominal aortic aneurysm, when combined with smoking status, can identify high-risk subgroups that may benefit from earlier or targeted screening, potentially improving the cost-effectiveness of national screening programs.
Main Result
Hazard Ratio: 3.7 (95% CI 2.86–4.8)
p-value: p=<0.001
Limitations
- Assumption that generating a PRS profile might not carry an additional cost
- UK Biobank has a healthy volunteer bias
- PRS contains only common genetic variants
- Study participants were restricted to individuals of European ancestry
Abstract
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 (R 2 ) 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.