Genomic prediction of coronary heart disease.
Authors | |
Abstract | AIMS: Genetics plays an important role in coronary heart disease (CHD) but the clinical utility of genomic risk scores (GRSs) relative to clinical risk scores, such as the Framingham Risk Score (FRS), is unclear. Our aim was to construct and externally validate a CHD GRS, in terms of lifetime CHD risk and relative to traditional clinical risk scores. METHODS AND RESULTS: We generated a GRS of 49 310 SNPs based on a CARDIoGRAMplusC4D Consortium meta-analysis of CHD, then independently tested it using five prospective population cohorts (three FINRISK cohorts, combined n = 12 676, 757 incident CHD events; two Framingham Heart Study cohorts (FHS), combined n = 3406, 587 incident CHD events). The GRS was associated with incident CHD (FINRISK HR = 1.74, 95% confidence interval (CI) 1.61-1.86 per S.D. of GRS; Framingham HR = 1.28, 95% CI 1.18-1.38), and was largely unchanged by adjustment for known risk factors, including family history. Integration of the GRS with the FRS or ACC/AHA13 scores improved the 10 years risk prediction (meta-analysis C-index: +1.5-1.6%, P CONCLUSIONS: A GRS based on a large number of SNPs improves CHD risk prediction and encodes different trajectories of lifetime risk not captured by traditional clinical risk scores. |
Year of Publication | 2016
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Journal | Eur Heart J
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Volume | 37
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Issue | 43
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Pages | 3267-3278
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Date Published | 2016 Nov 14
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ISSN | 1522-9645
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DOI | 10.1093/eurheartj/ehw450
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PubMed ID | 27655226
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PubMed Central ID | PMC5146693
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Links | |
Grant list | R01 HL087676 / HL / NHLBI NIH HHS / United States
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