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Marginal role for 53 common genetic variants in cardiovascular disease prediction

Morris, RW and Cooper, JA and Shah, T and Wong, A and Drenos, F and Engmann, J and McLachlan, S and Jefferis, B and Dale, C and Hardy, R and Kuh, D and Ben-Shlomo, Y and Wannamethee, SG and Whincup, PH and Casas, JP and Kivimaki, M and Kumari, M and Talmud, PJ and Price, JF and Dudbridge, F and Hingorani, AD and Humphries, SE (2016) 'Marginal role for 53 common genetic variants in cardiovascular disease prediction.' Heart, 102 (20). 1640 - 1647. ISSN 1355-6037

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Abstract

© 2016 Published by the BMJ Publishing Group Limited. 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
Subjects: H Social Sciences > H Social Sciences (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Jim Jamieson
Date Deposited: 22 Nov 2016 14:50
Last Modified: 23 Jan 2019 01:15
URI: http://repository.essex.ac.uk/id/eprint/18164

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