Development of the VISAGE enhanced tool and statistical models for epigenetic age estimation in blood, buccal cells and bones

Anna Woźniak, Antonia Heidegger, Danuta Piniewska-Róg, Ewelina Pośpiech, Catarina Xavier, Aleksandra Pisarek, Ewa Kartasińska, Michał Boroń, Ana Freire-Aradas, Marta Wojtas, Maria de la Puente, Harald Niederstätter, Rafał Płoski, Magdalena Spólnicka, Manfred Kayser, Christopher Phillips, Walther Parson, Wojciech Branicki*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

DNA methylation is known as a biomarker for age with applications in forensics. Here we describe the VISAGE (VISible Attributes through GEnomics) Consortium’s enhanced tool for epigenetic age estimation in somatic tissues. The tool is based on eight DNA methylation markers (44 CpGs), bisulfite multiplex PCR followed by sequencing on the MiSeq FGx platform, and three statistical prediction models for blood, buccal cells and bones. The model for blood is based on six CpGs from ELOVL2, MIR29B2CHG, KLF14, FHL2, TRIM59 and PDE4C, and predicts age with a mean absolute error (MAE) of 3.2 years, while the model for buccal cells includes five CpGs from PDE4C, MIR29B2CHG, ELOVL2, KLF14 and EDARADD and predicts age with MAE of 3.7 years, and the model for bones has six CpGs from ELOVL2, KLF14, PDE4C and ASPA and predicts age with MAE of 3.4 years. The VISAGE enhanced tool for age estimation in somatic tissues enables reliable collection of DNA methylation data from small amounts of DNA using a sensitive multiplex MPS assay that provides accurate estimation of age in blood, buccal swabs, and bones using the statistical model tailored to each tissue.

Original languageEnglish
Pages (from-to)6459-6484
Number of pages26
JournalAging
Volume13
Issue number5
DOIs
Publication statusPublished - 15 Mar 2021

Bibliographical note

Funding Information:
This study received support from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 740580 within the framework of the Visible Attributes through Genomics (VISAGE) Project and Consortium. MdlP was supported by a postdoctoral fellowship awarded by the Consellería de Cultura, Educación e Ordenación Universitaria and the Consellería de Economía, Emprego e Industria from Xunta de Galicia (Modalidade A, ED481B 2017/088). We would like to thank Martin Steinlechner and Burkhard Berger for their support (both Institute of Legal Medicine, Medical University of Innsbruck). Ana Freire-Aradas was supported by a postdoctorate grant funded by the Consellería de Cultura, Educación e Ordenación Universitaria e da Consellería de Economía, Emprego e Industria from Xunta de Galicia, Spain (Modalidade B, ED481B 2018/010).

Publisher Copyright:
© 2021 Woźniak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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