![]() ![]() Editor's evaluationĪlthough our genetic code does not change throughout our lives, our genes can be turned on and off as a result of epigenetics. These EpiScores for protein levels can therefore be a valuable resource for disease prediction and risk stratification. Notably, we found that our diabetes-associated EpiScores highlighted previous top biomarker associations from proteome-wide assessments of diabetes. These associations were largely independent of immune cell proportions, common lifestyle and health factors, and biological aging. By projecting these EpiScores into an independent sample (Generation Scotland n = 9537) and relating them to incident morbidities over a follow-up of 14 years, we uncovered 137 EpiScore-disease associations. Using data from four cohorts, we trained and tested epigenetic scores (EpiScores) for 953 plasma proteins, identifying 109 scores that explained between 1% and 58% of the variance in protein levels after adjusting for known protein quantitative trait loci (pQTL) genetic effects. Here, we leverage epigenome-wide data to study links between the DNA methylation (DNAm) signatures of the circulating proteome and incident diseases. However, characterising epigenetic influences could further inform disease predictions. Protein biomarkers have been identified across many age-related morbidities. Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, United Kingdom.Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, United Kingdom.Institute for Molecular Bioscience, University of Queensland, Australia.German Centre for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Max Planck Institute of Heart and Lung Research, Germany.Scientific Service Group Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, W.G.German Center for Diabetes Research (DZD), Germany.German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Germany.Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Germany.Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Germany.Population Research Center, The University of Texas at Austin, United States.Department of Psychology, The University of Texas at Austin, United States.Department of Psychiatry, University of Oxford, United Kingdom.Centre for Clinical Brain Sciences, Chancellor’s Building, University of Edinburgh, United Kingdom.Lothian Birth Cohorts, University of Edinburgh, United Kingdom.Department of Psychology, University of Edinburgh, United Kingdom.Computer Engineering Department, Virginia Tech, United States.Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, Qatar.Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, United Kingdom. ![]()
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