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Title: Marginal role for 53 common genetic variants in cardiovascular disease prediction
Authors: Morris, Richard W.
Cooper, Jackie A.
Shah, Tina
Wong, Andrew
Drenos, Fotios
Engmann, Jorgen
McLachlan, Stela
Jefferis, Barbara
Dale, Caroline
Hardy, Rebecca
Kuh, Diana
Ben-Shlomo, Yoav
Wannamethee, S. Goya
Whincup, Peter H.
Casas, Juan-Pablo
Kivimaki, Mika
Kumari, Meena
Talmud, Philippa J.
Price, Jacqueline F.
Dudbridge, Frank
Hingorani, Aroon D.
Humphries, Steve E.
UCLEB Consortium
First Published: 30-Jun-2016
Publisher: BMJ Publishing Group
Citation: Heart, 2016, 102 (20), pp. 1640-1647
Abstract: 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 10 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.
DOI Link: 10.1136/heartjnl-2016-309298
ISSN: 1355-6037
eISSN: 1468-201X
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Health Sciences

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