Marginal role for 53 common genetic variants in cardiovascular disease prediction. Issue 20 (30th June 2016)

• Record Type: Journal Article
• 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
• Is Part Of: Heart. Volume 102:Issue 20(2016)
• Page Start: 1640
• Page End: 1647
• Publication Date: 2016-06-30
• Subjects: Heart -- Diseases -- Treatment -- Periodicals; Cardiology -- Periodicals; 616.12
• DOI: 10.1136/heartjnl-2016-309298
• Languages: English
• ISSNs: 1355-6037

Abstract

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.