British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge, UK.
Nat Commun. 2024 Sep 14;15(1):8063. doi: 10.1038/s41467-024-52452-w.
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) 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.
由于腹主动脉瘤（AAA）的遗传性很高，且 AAA 与其他心血管疾病部分共享遗传结构，因此遗传信息可以帮助制定 AAA 筛查策略。通过利用多效性并对来自大型研究的汇总数据进行荟萃分析，我们构建了用于 AAA 的多基因风险评分（PRS）。利用相关特征，PRS 的性能（R）相对于仅使用 AAA 提高了 22.7%。与低 PRS 三分位相比，中三分位和高三分位的 AAA 风险比分别为 2.13（95%CI 1.61, 2.82）和 3.70（95%CI 2.86, 4.80），调整了临床危险因素。通过模拟建模，我们将 PRS 和吸烟分层筛查与仅邀请 65 岁以上男性且不邀请女性（当前英国策略）进行了比较。在一个未来可以获得基因组信息的情景中，我们的模型表明，邀请携带高 PRS 的男性当前吸烟者早于 65 岁，以及分别在 65 岁和 70 岁时对携带高/中 PRS 的女性吸烟者进行筛查，可能会提高成本效益。
