Development and validation of DNA methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes.

Autor: Cheng Y; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland., Gadd DA; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Gieger C; Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; German Center for Diabetes Research, München-Neuherberg, Germany., Monterrubio-Gómez K; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Zhang Y; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Berta I; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Stam MJ; School of Informatics, University of Edinburgh, Edinburgh, UK., Szlachetka N; School of Informatics, University of Edinburgh, Edinburgh, UK., Lobzaev E; School of Informatics, University of Edinburgh, Edinburgh, UK., Wrobel N; Edinburgh Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, UK., Murphy L; Edinburgh Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, UK., Campbell A; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Nangle C; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Walker RM; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh BioQuarter, Edinburgh, UK., Fawns-Ritchie C; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.; Department of Psychology, University of Edinburgh, Edinburgh, UK., Peters A; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; German Center for Diabetes Research, München-Neuherberg, Germany.; German Centre for Cardiovascular Research, Partner Site Munich Heart Alliance, München, Germany., Rathmann W; German Center for Diabetes Research, München-Neuherberg, Germany.; Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany., Porteous DJ; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Evans KL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., McIntosh AM; Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK., Cannings TI; School of Mathematics, University of Edinburgh, Edinburgh, UK., Waldenberger M; Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Ganna A; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland., McCartney DL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK., Vallejos CA; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. catalina.vallejos@ed.ac.uk.; The Alan Turing Institute, London, UK. catalina.vallejos@ed.ac.uk., Marioni RE; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. riccardo.marioni@ed.ac.uk.
Jazyk: angličtina
Zdroj: Nature aging [Nat Aging] 2023 Apr; Vol. 3 (4), pp. 450-458. Date of Electronic Publication: 2023 Apr 06.
DOI: 10.1038/s43587-023-00391-4
Abstrakt: Type 2 diabetes mellitus (T2D) presents a major health and economic burden that could be alleviated with improved early prediction and intervention. While standard risk factors have shown good predictive performance, we show that the use of blood-based DNA methylation information leads to a significant improvement in the prediction of 10-year T2D incidence risk. Previous studies have been largely constrained by linear assumptions, the use of cytosine-guanine pairs one-at-a-time and binary outcomes. We present a flexible approach (via an R package, MethylPipeR) based on a range of linear and tree-ensemble models that incorporate time-to-event data for prediction. Using the Generation Scotland cohort (training set n cases  = 374, n controls  = 9,461; test set n cases  = 252, n controls  = 4,526) our best-performing model (area under the receiver operating characteristic curve (AUC) = 0.872, area under the precision-recall curve (PRAUC) = 0.302) showed notable improvement in 10-year onset prediction beyond standard risk factors (AUC = 0.839, precision-recall AUC = 0.227). Replication was observed in the German-based KORA study (n = 1,451, n cases  = 142, P = 1.6 × 10 -5 ).
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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