Research Paper Volume 13, Issue 15 pp 19145—19164
Epigenetic age prediction in semen – marker selection and model development
- 1 Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland
- 2 Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck, Austria
- 3 Department of Data Science and Engineering, The Silesian University of Technology, Gliwice, Poland
- 4 Department of Legal Medicine, Medical College, Krakow, Poland
- 5 Department of Genetic Identification, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- 6 Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany
- 7 The Fertility Partnership Macierzynstwo, Krakow, Poland
- 8 PARENS Fertility Centre, Krakow, Poland
- 9 Central Forensic Laboratory of the Police, Warsaw, Poland
- 10 Department of Legal Medicine, Santiago de Compostela, Spain
- 11 Forensic Science Program, The Pennsylvania State University, University Park, PA 16802, USA
Received: March 16, 2021 Accepted: July 17, 2021 Published: August 10, 2021
https://doi.org/10.18632/aging.203399How to Cite
Copyright: © 2021 Pisarek 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.
Abstract
DNA methylation analysis is becoming increasingly useful in biomedical research and forensic practice. The discovery of differentially methylated sites (DMSs) that continuously change over an individual’s lifetime has led to breakthroughs in molecular age estimation. Although semen samples are often used in forensic DNA analysis, previous epigenetic age prediction studies mainly focused on somatic cell types. Here, Infinium MethylationEPIC BeadChip arrays were applied to semen-derived DNA samples, which identified numerous novel DMSs moderately correlated with age. Validation of the ten most age-correlated novel DMSs and three previously known sites in an independent set of semen-derived DNA samples using targeted bisulfite massively parallel sequencing, confirmed age-correlation for nine new and three previously known markers. Prediction modelling revealed the best model for semen, based on 6 CpGs from newly identified genes SH2B2, EXOC3, IFITM2, and GALR2 as well as the previously known FOLH1B gene, which predict age with a mean absolute error of 5.1 years in an independent test set. Further increases in the accuracy of age prediction from semen DNA will require technological progress to allow sensitive, simultaneous analysis of a much larger number of age correlated DMSs from the compromised DNA typical of forensic semen stains.