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Marginal role for 53 common genetic variants in cardiovascular disease prediction

Morris, Richard W and Cooper, Jackie A and Shah, Tina and Wong, Andrew and Drenos, Fotios and Engmann, Jorgen and McLachlan, Stela and Jefferis, Barbara and Dale, Caroline and Hardy, Rebecca and Kuh, Diana and Ben-Shlomo, Yoav and Wannamethee, S Goya and Whincup, Peter H and Casas, Juan-Pablo and Kivimaki, Mika and Kumari, Meena and Talmud, Philippa J and Price, Jacqueline F and Dudbridge, Frank and Hingorani, Aroon D and Humphries, Steve E (2016) 'Marginal role for 53 common genetic variants in cardiovascular disease prediction.' Heart, 102 (20). pp. 1640-1647. ISSN 1355-6037

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Objective We investigated discrimination and calibration of cardiovascular disease (CVD) risk scores when genotypic was added to phenotypic information. The potential of genetic information for those at intermediate risk by a phenotype-based risk score was assessed. Methods Data were from seven prospective studies including 11..851 individuals initially free of CVD or diabetes, with 1444 incident CVD events over 10â..years' follow-up. We calculated a score from 53 CVD-related single nucleotide polymorphisms and an established CVD risk equation QRISK-2' comprising phenotypic measures. The area under the receiver operating characteristic curve (AUROC), detection rate for given false-positive rate (FPR) and net reclassification improvement (NRI) index were estimated for gene scores alone and in addition to the QRISK-2 CVD risk score. We also evaluated use of genetic information only for those at intermediate risk according to QRISK-2. Results The AUROC was 0.635 for QRISK-2 alone and 0.623 with addition of the gene score. The detection rate for 5% FPR improved from 11.9% to 12.0% when the gene score was added. For a 10-year CVD risk cut-off point of 10%, the NRI was 0.25% when the gene score was added to QRISK-2. Applying the genetic risk score only to those with QRISK-2 risk of 10%-<20% and prescribing statins where risk exceeded 20% suggested that genetic information could prevent one additional event for every 462 people screened. Conclusion The gene score produced minimal incremental population-wide utility over phenotypic risk prediction of CVD. Tailored prediction using genetic information for those at intermediate risk may have clinical utility.

Item Type: Article
Uncontrolled Keywords: UCLEB Consortium; Humans; Cardiovascular Diseases; Genetic Predisposition to Disease; Genetic Markers; False Positive Reactions; Incidence; Area Under Curve; Risk Assessment; Risk Factors; Prospective Studies; Reproducibility of Results; Predictive Value of Tests; ROC Curve; Gene Expression Profiling; Phenotype; Polymorphism, Single Nucleotide; Time Factors; Adult; Middle Aged; Female; Male; Genetic Association Studies; United Kingdom
Subjects: H Social Sciences > H Social Sciences (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences
Faculty of Social Sciences > Institute for Social and Economic Research
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 22 Nov 2016 14:50
Last Modified: 06 Jan 2022 14:41

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