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

Sci Rep. 2020 Sep 24;10(1):15652. doi: 10.1038/s41598-020-72567-6.

Abstract

Several blood-based age prediction models have been developed using less than a dozen to more than a hundred DNA methylation biomarkers. Only one model (Z-P1) based on pyrosequencing has been developed using DNA methylation of a single locus located in the ELOVL2 promoter, which is considered as one of the best age-prediction biomarker. Although multi-locus models generally present better performances compared to the single-locus model, they require more DNA and present more inter-laboratory variations impacting the predictions. Here we developed 17,018 single-locus age prediction models based on DNA methylation of the ELOVL2 promoter from pooled data of four different studies (training set of 1,028 individuals aged from 0 and 91 years) using six different statistical approaches and testing every combination of the 7 CpGs, aiming to improve the prediction performances and reduce the effects of inter-laboratory variations. Compared to Z-P1 model, three statistical models with the optimal combinations of CpGs presented improved performances (MAD of 4.41-4.77 in the testing set of 385 individuals) and no age-dependent bias. In an independent testing set of 100 individuals (19-65 years), we showed that the prediction accuracy could be further improved by using different CpG combinations and increasing the number of technical replicates (MAD of 4.17).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / blood*
  • Aging / genetics*
  • Child
  • Child, Preschool
  • CpG Islands / genetics
  • DNA Methylation*
  • Fatty Acid Elongases / genetics*
  • Female
  • Genetic Loci / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Laboratories*
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics*
  • Young Adult

Substances

  • ELOVL2 protein, human
  • Fatty Acid Elongases