Marginal role for 53 common genetic variants in cardiovascular disease prediction.

Morris, RW; Cooper, JA; Shah, T; Wong, A; Drenos, F; Engmann, J; McLachlan, S; Jefferis, B; Dale, C; Hardy, R; +13 more...Kuh, D; Ben-Shlomo, Y; Wannamethee, SG; Whincup, PH; Casas, J; Kivimaki, M; Kumari, M; Talmud, PJ; Price, JF; Dudbridge, FORCID logo; Hingorani, AD; Humphries, SE; UCLEB Consortium and (2016) Marginal role for 53 common genetic variants in cardiovascular disease prediction. Heart (British Cardiac Society), 102 (20). pp. 1640-1647. ISSN 1355-6037 DOI: 10.1136/heartjnl-2016-309298
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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 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.


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