作者
Danni A Gadd, Robert F Hillary, Daniel L McCartney, Shaza B Zaghlool, Anna J Stevenson, Yipeng Cheng, Chloe Fawns-Ritchie, Cliff Nangle, Archie Campbell, Robin Flaig, Sarah E Harris, Rosie M Walker, Liu Shi, Elliot M Tucker-Drob, Christian Gieger, Annette Peters, Melanie Waldenberger, Johannes Graumann, Allan F McRae, Ian J Deary, David J Porteous, Caroline Hayward, Peter M Visscher, Simon R Cox, Kathryn L Evans, Andrew M McIntosh, Karsten Suhre, Riccardo E Marioni
发表日期
2022/1/13
期刊
Elife
卷号
11
页码范围
e71802
出版商
eLife Sciences Publications Limited
简介
Protein biomarkers have been identified across many age-related morbidities. However, characterising epigenetic influences could further inform disease predictions. Here, we leverage epigenome-wide data to study links between the DNA methylation (DNAm) signatures of the circulating proteome and incident diseases. 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. 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 130 EpiScore-disease associations. These associations were largely independent of immune cell proportions, common lifestyle and health factors, and biological aging. Notably, we found that our diabetes-associated EpiScores highlighted previous top biomarker associations from proteome-wide assessments of diabetes. These EpiScores for protein levels can therefore be a valuable resource for disease prediction and risk stratification.
引用总数