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• W4309847981 abstract "Abdominal aortic aneurysms (AAA) are common enlargements of the abdominal aorta which can grow larger until rupture, often leading to death. Detection of AAA is often by ultrasonography and screening recommendations are mostly directed at men over 65 with a smoking history. Recent large-scale genome-wide association studies have identified genetic loci associated with AAA risk. We combined known risk factors, polygenic risk scores (PRS) and precedent clinical diagnoses from electronic health records (EHR) to develop predictive models for AAA, and compared performance against screening recommendations. The PRS included genome-wide summary statistics from the Million Veteran Program and FinnGen (10,467 cases, 378,713 controls of European ancestry), with optimization in Vanderbilt's BioVU and validated in the eMERGE Network, separately across both White and Black participants. Candidate diagnoses were identified through a temporally-oriented Phenome-wide association study in independent EHR data from Vanderbilt, and features were selected via elastic net. We calculated C-statistics in eMERGE for models including PRS, phecodes, and covariates using regression weights from BioVU. The AUC for the full model in the test set was 0.883 (95% CI 0.873-0.892), 0.844 (0.836-0.851) for covariates only, 0.613 (95% CI 0.604-0.622) when using primary USPSTF screening criteria, and 0.632 (95% CI 0.623-0.642) using primary and secondary criteria. Brier scores were between 0.003 and 0.023 for our models indicating good calibration, and net reclassification improvement over combined primary and secondary USPSTF criteria was 0.36-0.60. We provide PRS for AAA which are strongly associated with AAA risk and add to predictive model performance. These models substantially improve identification of people at risk of a AAA diagnosis compared with existing guidelines, with evidence of potential applicability in minority populations." @default.
• W4309847981 created "2022-11-29" @default.
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• W4309847981 date "2022-11-01" @default.
• W4309847981 modified "2023-10-14" @default.
• W4309847981 title "Predictive models for abdominal aortic aneurysms using polygenic scores and PheWAS-derived risk factors" @default.
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• W4309847981 doi "https://doi.org/10.1142/9789811270611_0039" @default.
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• W4309847981 hasPublicationYear "2022" @default.
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