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.
Highlights
The use of epigenome-wide association studies has provided a deeper insight into individual differences and fluctuations in DNA methylation levels in the human genome
DNA-based age prediction in forensic applications can be used for intelligence purposes to gain information from unknown individuals who have left their DNA at a crime scene or whose remains are subjected to genetic identification
Eight age-informative DNA methylation markers containing 44 CpG sites (Supplementary Table 1) were selected from the literature based on their reported age correlation in different somatic tissues such as blood, buccal cells and bones [11, 12, 27,28,29,30,31], and were successfully combined into one multiplex PCR assay for bisulfite-converted DNA
Summary
The use of epigenome-wide association studies has provided a deeper insight into individual differences and fluctuations in DNA methylation levels in the human genome. Many studies have identified agerelated differentially methylated regions (DMRs) and sites (DMSs) that have the potential to predict epigenetic age in various human tissues [e.g. 1–4]. These studies indicated that epigenetic age is highly www.aging-us.com correlated with chronological age but have revealed differences in epigenetic aging rates amongst individuals. Forensic DNA phenotyping has emerged as an approach that can obtain information of an unknown crime scene sample donor on their appearance and bio-geographic ancestry from crime scene DNA [9] This allows for focused police investigations to help characterize unknown perpetrators, where estimating age from crime scene DNA would be highly informative. Reliable DNA-based prediction of appearance traits as a forensic intelligence tool is ideally accompanied with age estimation
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