Epigenetic Contributions to Clinical Risk Prediction of Cardiovascular Disease.
| Autor: | Chybowska AD; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (A.D.C., D.A.G., Y.C., E.B., A.C., D.L.M., K.L.E., R.E.M.), The University of Edinburgh, United Kingdom., Gadd DA; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (A.D.C., D.A.G., Y.C., E.B., A.C., D.L.M., K.L.E., R.E.M.), The University of Edinburgh, United Kingdom., Cheng Y; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (A.D.C., D.A.G., Y.C., E.B., A.C., D.L.M., K.L.E., R.E.M.), The University of Edinburgh, United Kingdom., Bernabeu E; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (A.D.C., D.A.G., Y.C., E.B., A.C., D.L.M., K.L.E., R.E.M.), The University of Edinburgh, United Kingdom., Campbell A; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (A.D.C., D.A.G., Y.C., E.B., A.C., D.L.M., K.L.E., R.E.M.), The University of Edinburgh, United Kingdom., Walker RM; School of Psychology, University of Exeter, United Kingdom (R.M.W.)., McIntosh AM; Division of Psychiatry, Royal Edinburgh Hospital (A.M.M.), The University of Edinburgh, United Kingdom., Wrobel N; Edinburgh Clinical Research Facility, Western General Hospital (N.W., L.M.), The University of Edinburgh, United Kingdom., Murphy L; Edinburgh Clinical Research Facility, Western General Hospital (N.W., L.M.), The University of Edinburgh, United Kingdom., Welsh P; Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (P.W., N.S.)., Sattar N; Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (P.W., N.S.)., Price JF; Usher Institute, Old Medical School (J.F.P.), The University of Edinburgh, United Kingdom., McCartney DL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (A.D.C., D.A.G., Y.C., E.B., A.C., D.L.M., K.L.E., R.E.M.), The University of Edinburgh, United Kingdom., Evans KL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (A.D.C., D.A.G., Y.C., E.B., A.C., D.L.M., K.L.E., R.E.M.), The University of Edinburgh, United Kingdom., Marioni RE; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (A.D.C., D.A.G., Y.C., E.B., A.C., D.L.M., K.L.E., R.E.M.), The University of Edinburgh, United Kingdom. |
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| Jazyk: | angličtina |
| Zdroj: | Circulation. Genomic and precision medicine [Circ Genom Precis Med] 2024 Feb; Vol. 17 (1), pp. e004265. Date of Electronic Publication: 2024 Jan 30. |
| DOI: | 10.1161/CIRCGEN.123.004265 |
| Abstrakt: | Background: Cardiovascular disease (CVD) is among the leading causes of death worldwide. The discovery of new omics biomarkers could help to improve risk stratification algorithms and expand our understanding of molecular pathways contributing to the disease. Here, ASSIGN-a cardiovascular risk prediction tool recommended for use in Scotland-was examined in tandem with epigenetic and proteomic features in risk prediction models in ≥12 657 participants from the Generation Scotland cohort. Methods: Previously generated DNA methylation-derived epigenetic scores (EpiScores) for 109 protein levels were considered, in addition to both measured levels and an EpiScore for cTnI (cardiac troponin I). The associations between individual protein EpiScores and the CVD risk were examined using Cox regression (n Results: Sixty-five protein EpiScores were associated with incident CVD independently of ASSIGN and the measured concentration of cTnI ( P <0.05), over a follow-up of up to 16 years of electronic health record linkage. The most significant EpiScores were for proteins involved in metabolic, immune response, and tissue development/regeneration pathways. A composite CVD EpiScore (based on 45 protein EpiScores) was a significant predictor of CVD risk independent of ASSIGN and the concentration of cTnI (hazard ratio, 1.32; P =3.7×10 -3 ; 0.3% increase in C-statistic). Conclusions: EpiScores for circulating protein levels are associated with CVD risk independent of traditional risk factors and may increase our understanding of the etiology of the disease. Competing Interests: Disclosures L. Murphy and Dr Marioni received a speaker fee from Illumina. Dr Marioni is an advisor to the Epigenetic Clock Development Foundation. D.A. Gadd and Dr Marioni received consultancy fees from Optima Partners. The other authors report no conflicts. |
| Databáze: | MEDLINE |
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