title: Development of a methylation marker set for forensic age estimation using analysis of public methylation data and the Agena Bioscience EpiTYPER system.
abstract: Individual age estimation has the potential to provide key information that could enhance and extend DNA intelligence tools. Following predictive tests for externally visible characteristics developed in recent years, prediction of age could guide police investigations and improve the assessment of age-related phenotype expression patterns such as hair colour changes and early onset of male pattern baldness. DNA methylation at CpG positions has emerged as the most promising DNA tests to ascertain the individual age of the donor of a biological contact trace. Although different methodologies are available to detect DNA methylation, EpiTYPER technology (Agena Bioscience, formerly Sequenom) provides useful characteristics that can be applied as a discovery tool in localized regions of the genome. In our study, a total of twenty-two candidate genomic regions, selected from the assessment of publically available data from the Illumina HumanMethylation 450 BeadChip, had a total of 177 CpG sites with informative methylation patterns that were subsequently investigated in detail. From the methylation analyses made, a novel age prediction model based on a multivariate quantile regression analysis was built using the seven highest age-correlated loci of ELOVL2, ASPA, PDE4C, FHL2, CCDC102B, C1orf132 and chr16:85395429. The detected methylation levels in these loci provide a median absolute age prediction error of ±3.07years and a percentage of prediction error relative to the age of 6.3%. We report the predictive performance of the developed model using cross validation of a carefully age-graded training set of 725 European individuals and a test set of 52 monozygotic twin pairs. The multivariate quantile regression age predictor, using the CpG sites selected in this study, has been placed in the open-access Snipper forensic classification website.
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Spain. Electronic address: ana.freire@usc.es.
authors.forename: A
authors.initials: A
authors.lastname: Freire-Aradas
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Phillips
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Mosquera-Miguel
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Girón-Santamaría
authors.affiliation: Faculty of Mathematics, University of Santiago de Compostela, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gómez-Tato
authors.affiliation: Faculty of Mathematics, University of Santiago de Compostela, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Casares de Cal
authors.affiliation: Faculty of Mathematics, University of Santiago de Compostela, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Álvarez-Dios
authors.affiliation: Spanish National Genotyping Center-USC-PRB2-ISCIII, Santiago de Compostela, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ansede-Bermejo
authors.affiliation: Spanish National Genotyping Center-USC-PRB2-ISCIII, Santiago de Compostela, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Torres-Español
authors.affiliation: Institute of Legal Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany.
authors.forename: P M
authors.initials: PM
authors.lastname: Schneider
authors.affiliation: Institute of Zoology, Faculty of Biology and Earth Sciences, Jagiellonian University, Krakow, Poland; Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Pośpiech
authors.affiliation: Malopolska Centre of Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Branicki
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Spain; Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Á
authors.initials: Á
authors.lastname: Carracedo
authors.affiliation: Forensic Genetics Unit, Institute of Forensic Sciences, University of Santiago de Compostela, Spain.
authors.forename: M V
authors.initials: MV
authors.lastname: Lareu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D056426:Genetic Loci; D005819:Genetic Markers; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D012984:Software; D014430:Twins, Monozygotic / Q000235:genetics; D055815:Young Adult
chemical_list: D005819:Genetic Markers
keywords: Agena Bioscience EpiTYPER; CpG sites; DNA methylation; Forensic age estimation; Illumina HumanMethylation 450K; Multivariate quantile regression