Development and validation of DNA methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes
dc.contributor.author | Cheng, Y | |
dc.contributor.author | Gadd, DA | |
dc.contributor.author | Gieger, C | |
dc.contributor.author | Monterrubio-Gómez, K | |
dc.contributor.author | Zhang, Y | |
dc.contributor.author | Berta, I | |
dc.contributor.author | Stam, MJ | |
dc.contributor.author | Szlachetka, N | |
dc.contributor.author | Lobzaev, E | |
dc.contributor.author | Wrobel, N | |
dc.contributor.author | Murphy, L | |
dc.contributor.author | Campell, A | |
dc.contributor.author | Nangle, C | |
dc.contributor.author | Walker, RM | |
dc.contributor.author | Fawns-Ritchie, C | |
dc.contributor.author | Peters, A | |
dc.contributor.author | Rathmann, W | |
dc.contributor.author | Porteous, DJ | |
dc.contributor.author | Evans, KL | |
dc.contributor.author | McIntosh, AM | |
dc.contributor.author | Cannings, TI | |
dc.contributor.author | Waldenberger, M | |
dc.contributor.author | Ganna, A | |
dc.contributor.author | McCartney, DL | |
dc.contributor.author | Vallejos, CA | |
dc.contributor.author | Marioni, RE | |
dc.date.accessioned | 2023-03-29T09:56:13Z | |
dc.date.issued | 2023-04-06 | |
dc.date.updated | 2023-03-29T09:23:31Z | |
dc.description.abstract | 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 CpGs one-at43 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 ncases=374, ncontrols=9,461; test set ncases=252, ncontrols=4,526) our best-performing model (Area Under the Curve (AUC)=0.872, Precision Recall AUC (PRAUC)=0.302) showed notable improvement in 10-year onset prediction beyond standard risk factors (AUC=0.839, PRAUC=0.227). Replication was observed in the German-based KORA study (n=1,451, ncases = 142, p=1.6x10-5 49 ). | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Chief Scientist Office of the Scottish Government Health Directorates | en_GB |
dc.description.sponsorship | Scottish Funding Council | en_GB |
dc.description.sponsorship | Brain & Behavior Research Foundation | |
dc.description.sponsorship | Royal College of Physicians of Edinburgh | |
dc.description.sponsorship | University of Edinburgh | |
dc.description.sponsorship | University of Helsinki | |
dc.description.sponsorship | Alzheimer’s Research UK | |
dc.description.sponsorship | UKRI | |
dc.identifier.citation | Vol. 3, pp. 450–458 | en_GB |
dc.identifier.doi | 10.1038/s43587-023-00391-4 | |
dc.identifier.grantnumber | 104036/Z/14/Z | en_GB |
dc.identifier.grantnumber | 108890/Z/15/Z | en_GB |
dc.identifier.grantnumber | 216767/Z/19/Z | en_GB |
dc.identifier.grantnumber | CZD/16/6 | en_GB |
dc.identifier.grantnumber | HR03006 | en_GB |
dc.identifier.grantnumber | 27404 | |
dc.identifier.grantnumber | 108890/Z/15/Z | |
dc.identifier.grantnumber | ARUK-PG2017B-10 | |
dc.identifier.grantnumber | AS-PG-19b-010 | |
dc.identifier.grantnumber | EP/S02431X/1 | |
dc.identifier.uri | http://hdl.handle.net/10871/132801 | |
dc.identifier | ORCID: 0000-0002-1060-4479 (Walker, Rosie May) | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Research | en_GB |
dc.relation.url | https://epi.helmholtz-muenchen.de/ | en_GB |
dc.relation.url | https://github.com/marioni-group/episcores-diabetes-prediction | |
dc.relation.url | https://doi.org/10.5281/zenodo.7628959 | |
dc.relation.url | https://github.com/marioni-group/MethylPipeR | |
dc.relation.url | https://doi.org/10.5281/zenodo.7628816 | |
dc.relation.url | https://github.com/marioni-group/MethylPipeR-UI | |
dc.relation.url | https://doi.org/10.5281/zenodo.7635952 | |
dc.rights | © The Author(s), under exclusive licence to Springer Nature America, Inc. 2023. This research was funded in whole, or in part, by the Wellcome Trust [104036/Z/14/Z, 108890/Z/15/Z, 216767/Z/19/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. | |
dc.title | Development and validation of DNA methylation scores in two European cohorts augment 10-year risk prediction of type 2 diabetes | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-03-29T09:56:13Z | |
dc.identifier.issn | 2662-8465 | |
dc.description | This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record | en_GB |
dc.description | Data availability: According to the terms of consent for Generation Scotland participants, access to data must be reviewed by the Generation Scotland Access Committee. Applications should be made to access@generationscotland.org. The informed consent given by the KORA S4 study participants does not cover data posting in public databases. However, data are available upon request from the KORA Project Application Self-Service Tool (https://epi.helmholtz-muenchen.de/). Data requests can be submitted online and are subject to approval by the KORA board. | en_GB |
dc.description | Code availability: Analysis scripts for this study are available at https://github.com/marioni-group/episcores-diabetes-prediction and https://doi.org/10.5281/zenodo.7628959. MethylPipeR v.0.1.0 is available at https://github.com/marioni-group/MethylPipeR and https://doi.org/10.5281/zenodo.7628816. MethylPipeR-UI is available at https://github.com/marioni-group/MethylPipeR-UI and https://doi.org/10.5281/zenodo.7635952. | |
dc.identifier.journal | Nature Aging | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-02-27 | |
dcterms.dateSubmitted | 2021-11-19 | |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2023-01-06 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-03-29T09:23:40Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2023-07-27T14:30:09Z | |
refterms.panel | A | en_GB |
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Inc. 2023. This research was funded in whole, or in part, by the Wellcome Trust [104036/Z/14/Z, 108890/Z/15/Z, 216767/Z/19/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.