Evaluating the cost-effectiveness of polygenic risk score-stratified screening for abdominal aortic aneurysm
Abstract As the heritability of abdominal aortic aneurysm (AAA) is high and AAA partially shares genetic architecture with other cardiovascular diseases, there is interest in whether genetic information could inform AAA screening strategies. Exploiting pleiotropy and meta-analysing summary data from large AAA studies, we constructed a polygenic risk score (PRS) for AAA. Compared with the low PRS tertile, the intermediate and high PRS tertiles had hazard ratios for AAA of 2.13 (95%CI 1.61, 2.82) and 3.70 (95%CI 2.86, 4.80) respectively, after adjusting for known clinical risk factors. Using simulation modelling, we compared 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 on the population, our modelling suggests inviting male current smokers with high PRS earlier than 65 and targeting screening in female smokers with high/intermediate PRS at 65 and 70 respectively, may improve cost-effectiveness..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 11. Dez. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kelemen, M. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.11.02.23297906 |
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| PPN (Katalog-ID): |
XBI041423623 |
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| 520 | |a Abstract As the heritability of abdominal aortic aneurysm (AAA) is high and AAA partially shares genetic architecture with other cardiovascular diseases, there is interest in whether genetic information could inform AAA screening strategies. Exploiting pleiotropy and meta-analysing summary data from large AAA studies, we constructed a polygenic risk score (PRS) for AAA. Compared with the low PRS tertile, the intermediate and high PRS tertiles had hazard ratios for AAA of 2.13 (95%CI 1.61, 2.82) and 3.70 (95%CI 2.86, 4.80) respectively, after adjusting for known clinical risk factors. Using simulation modelling, we compared 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 on the population, our modelling suggests inviting male current smokers with high PRS earlier than 65 and targeting screening in female smokers with high/intermediate PRS at 65 and 70 respectively, may improve cost-effectiveness. | ||
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