title: Development of a forensically useful age prediction method based on DNA methylation analysis.
abstract: Forensic DNA phenotyping needs to be supplemented with age prediction to become a relevant source of information on human appearance. Recent progress in analysis of the human methylome has enabled selection of multiple candidate loci showing linear correlation with chronological age. Practical application in forensic science depends on successful validation of these potential age predictors. In this study, eight DNA methylation candidate loci were analysed using convenient and reliable pyrosequencing technology. A total number of 41 CpG sites was investigated in 420 samples collected from men and women aged from 2 to 75 years. The study confirmed correlation of all the investigated markers with human age. The five most significantly correlated CpG sites in ELOVL2 on 6p24.2, C1orf132 on 1q32.2, TRIM59 on 3q25.33, KLF14 on 7q32.3 and FHL2 on 2q12.2 were chosen to build a prediction model. This restriction allowed the technical analysis to be simplified without lowering the prediction accuracy significantly. Model parameters for a discovery set of 300 samples were R(2)=0.94 and the standard error of the estimate=4.5 years. An independent set of 120 samples was used to test the model performance. Mean absolute deviation for this testing set was 3.9 years. The number of correct predictions ±5 years achieved a very high level of 86.7% in the age category 2-19 and gradually decreased to 50% in the age category 60-75. The prediction model was deterministic for individuals belonging to these two extreme age categories. The developed method was implemented in a freely available online age prediction calculator.
authors.affiliation: Central Forensic Laboratory of the Police, Warsaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Zbieć-Piekarska
authors.affiliation: Central Forensic Laboratory of the Police, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Spólnicka
authors.affiliation: Institute of Forensic Research, Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kupiec
authors.affiliation: Institute of Forensic Research, Krakow, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Parys-Proszek
authors.affiliation: Central Forensic Laboratory of the Police, Warsaw, Poland.
authors.forename: Żanetta
authors.initials: Ż
authors.lastname: Makowska
authors.affiliation: Central Forensic Laboratory of the Police, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pałeczka
authors.affiliation: BioVectis, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kucharczyk
authors.affiliation: Warsaw Medical University, Warsaw, Poland.
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.affiliation: Institute of Forensic Research, Krakow, Poland; Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland. Electronic address: wbranicki@ies.krakow.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Branicki
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands; D004247:DNA / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D053803:Forensic Genetics / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: D004247:DNA
keywords: DNA methylation; DNA-based age prediction; Forensic science; Prediction modelling