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Bauer, Alina; Zierer, Astrid; Gieger, Christian; Büyüközkan, Mustafa; Müller-Nurasyid, Martina; Grallert, Harald; Meisinger, Christa; Strauch, Konstantin; Prokisch, Holger; Roden, Michael; Peters, Annette; Krumsiek, Jan; Herder, Christian; Koenig, Wolfgang; Thorand, Barbara; Huth, Cornelia (3. June 2021): Comparison of genetic risk prediction models to improve prediction of coronary heart disease in two large cohorts of the MONICA/KORA study. In: Genetic Epidemiology: pp. 1-18
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Abstract

It is still unclear how genetic information, provided as single-nucleotide polymorphisms (SNPs), can be most effectively integrated into risk prediction models for coronary heart disease (CHD) to add significant predictive value beyond clinical risk models. For the present study, a population-based case-cohort was used as a trainingset (451 incident cases, 1488 noncases) and an independent cohort as testset (160 incident cases, 2749 noncases). The following strategies to quantify genetic information were compared: A weighted genetic risk score including Metabochip SNPs associated with CHD in the literature (GRSMetabo ); selection of the most predictive SNPs among these literature-confirmed variants using priority-Lasso (PLMetabo ); validation of two comprehensive polygenic risk scores: GRSGola based on Metabochip data, and GRSKhera (available in the testset only) based on cross-validated genome-wide genotyping data. We used Cox regression to assess associations with incident CHD. C-index, category-free net reclassification index (cfNRI) and relative integrated discrimination improvement (IDIrel ) were used to quantify the predictive performance of genetic information beyond Framingham risk score variables. In contrast to GRSMetabo and PLMetabo , GRSGola significantly improved the prediction (delta C-index [95% confidence interval]: 0.0087 [0.0044, 0.0130]; IDIrel : 0.0509 [0.0131, 0.0894]; cfNRI improved only in cases: 0.1761 [0.0253, 0.3219]). GRSKhera yielded slightly worse prediction results than GRSGola .