Improved age determination of blood and teeth samples using a selected set of DNA methylation markers.
Age estimation from DNA methylation markers has seen an exponential growth of interest, not in the least from forensic scientists. The current published assays, however, can still be improved by lowering the number of markers in the assay and by providing more accurate models to predict chronological age. From the published literature we selected 4 age-associated genes (ASPA, PDE4C, ELOVL2, and EDARADD) and determined CpG methylation levels from 206 blood samples of both deceased and living individuals (age range: 0-91 years). This data was subsequently used to compare prediction accuracy with both linear and non-linear regression models. A quadratic regression model in which the methylation levels of ELOVL2 were squared showed the highest accuracy with a Mean Absolute Deviation (MAD) between chronological age and predicted age of 3.75 years and an adjusted R(2) of 0.95. No difference in accuracy was observed for samples obtained either from living and deceased individuals or between the 2 genders. In addition, 29 teeth from different individuals (age range: 19-70 years) were analyzed using the same set of markers resulting in a MAD of 4.86 years and an adjusted R(2) of 0.74. Cross validation of the results obtained from blood samples demonstrated the robustness and reproducibility of the assay. In conclusion, the set of 4 CpG DNA methylation markers is capable of producing highly accurate age predictions for blood samples from deceased and living individuals.
a KU Leuven - University of Leuven ; Department of Imaging & Pathology ; Leuven , Belgium.|b KU-Leuven - University of Leuven; University Hospitals Leuven; Department of Forensic Medicine; Laboratory of Forensic Genetics and Molecular Archeology ; Leuven , Belgium.
Bram
B
Bekaert
a KU Leuven - University of Leuven ; Department of Imaging & Pathology ; Leuven , Belgium.
Aubeline
A
Kamalandua
c Smithsonian Institution; NMNH; MRC112 ; Anthropology Department ; Washington, DC USA.
Sara C
SC
Zapico
a KU Leuven - University of Leuven ; Department of Imaging & Pathology ; Leuven , Belgium.|b KU-Leuven - University of Leuven; University Hospitals Leuven; Department of Forensic Medicine; Laboratory of Forensic Genetics and Molecular Archeology ; Leuven , Belgium.
Wim
W
Van de Voorde
a KU Leuven - University of Leuven ; Department of Imaging & Pathology ; Leuven , Belgium.|b KU-Leuven - University of Leuven; University Hospitals Leuven; Department of Forensic Medicine; Laboratory of Forensic Genetics and Molecular Archeology ; Leuven , Belgium.
Ronny
R
Decorte
D000123:Acetyltransferases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000366:Age Determination by Teeth; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics*; D000581:Amidohydrolases / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands / Q000235:genetics*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D053362:Edar-Associated Death Domain Protein / Q000235:genetics; D000081031:Fatty Acid Elongases; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged
C506125:EDARADD protein, human; C000630967:ELOVL2 protein, human; D053362:Edar-Associated Death Domain Protein; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517361:PDE4C protein, human; D000581:Amidohydrolases; C019751:aspartoacylase
CpG marker; DNA methylation; DNA-based age prediction; quadratic regression modeling