Evaluation of DNA methylation-based age prediction on blood

Abstract

DNA methylation has been increasingly recognised for its potential use in forensic age prediction. In this study, our prediction model based on three CpG sites in three methylation markers was able to predict age for liquid blood samples with a mean absolute deviation of 5 years. The overall prediction accuracy of our model was similar to a previously published model, reanalyzed in our study. Additionally, the present study examined age prediction from bloodstains recovered at Day 0 and Day 21 using reduced quantities of DNA.

Evaluation of six blood-based age prediction models using DNA methylation analysis by pyrosequencing

“…Of the six models, the Bekaert model presented the best overall performance and accuracy for age prediction (MAD of 4.5 and SEE of 6.8, Table 4) in our cohort of 100 French blood samples, closely followed by the Thong model (MAD of 5.2 and SEE of 7.2). Thus both models presented overall performances close to the original studies (MAD of 3.75 for the Bekaert model and 3.3–5 for the Thong model, Supplementary Table 4) 25,26 , suggesting small inter-laboratory variations.…”

“…The overall accuracy observed for the Zbiec-Piekarska 2 and Park models was among the lowest out of the six models tested (MAD of 7.2–8.7 and SEE of 9.2–10.3, Table 4), which contrasted with the better values of the performance indicators for these models in the original studies (MAD of 3.1–3.9 and SEE of 4.5–6.9, Supplementary Table 4) 21,28 . Two independent studies also evaluated the Zbiec-Piekarska 2 model and found a higher MAD (4.18 and 4.8) compared to the original study 26,29 , suggesting that inter-laboratory variability can influence the performance of a model. However, in our study, the models of Zbiec-Piekarska 2 and Park tended to systematically under- and over-estimate the predicted age compared to the chronological age (Fig.…”

“…It should also be noted that the majority of the models predict age according to a multivariate linear equation, with the exception of one model which relies on a multivariate quadratic equation as it considers a quadratic relationship between ELOVL2 DNA methylation and chronological age 25 . Other recurring DNA methylation-based, age prediction biomarkers used in different models include ASPA , KLF14 and TRIM59 22,25,26,28 .…”

“…While these blood-based age prediction models, which use DNA methylation analysis by pyrosequencing, all present a good level of age-prediction accuracy (mean absolute deviation from chronological age (MAD) of around 3–5 years) 17 , to date few have been evaluated in other studies by other laboratories 26,29 , and no study has evaluated and compared different models in the same population. Here we present an evaluation of six blood-based age prediction models using DNA methylation analysis by pyrosequencing on 100 blood samples from 100 French individuals aged from 19 to 65 years.…”

Improvements and inter-laboratory implementation and optimization of blood-based single-locus age prediction models using DNA methylation of the ELOVL2 promoter

“…To our knowledge only one blood-based age prediction model has been developed from a single locus located in the ELOVL2 promoter and used multiple linear regression 25 , while all the other models were developed as multi-locus models from at least two different loci 21 . In a recent study, we evaluated and inter-compared six-age prediction models on a cohort of 100 individuals aged from 19 to 65 years 26 , including a single-locus model (Zbiec-Piekarska 1 25 ) and five multi-locus models (Bekaert 27 , Park 28 , Thong 29 , Weidner 30 , and Zbiec-Piekarska 2 31 ). The models presenting the best age prediction accuracy were the multi-locus models of Bekaert and Thong (MAD of 4.5–5.2 years and SEE of 6.8–7.2 years) followed by the single-locus model of Zbiec-Piekarska 1 (MAD of 6.8 year and SEE of 8.6 years) while the models presenting the worst age prediction performances (MAD of 7.2–8.7 years and SEE of 9.2–10.3 years) were the three other multi-locus models of Weidner, Park and Zbiec-Piekarska 2 26 .…”