RT Journal Article
T1 Exploring legal age estimation using DNA methylation
A1 Boullón-Cassau, M.
A1 Ambroa-Conde, A.
A1 Casares de Cal, María de los Ángeles
A1 Gómez Tato, Antonio
A1 Mosquera Miguel, Ana
A1 Ruiz-Ramírez, J.
A1 Cabrejas-Olalla, A.
A1 González-Bao, J.
A1 Casanova Adán, Lucía
A1 Puente Vila, María del Carmen de la
A1 Rodríguez, A.
A1 Phillips, C.
A1 Lareu Huidobro, María Victoria
A1 Freire Aradas, Ana María
K1 DNA methylation
K1 Legal age
K1 Quantile regression
K1 Horvath’s skin & blood clock
AB Minors (subjects under the legal age, established at this study at 18 years) benefit from a series of legal rights created to protect them and guarantee their welfare. However, throughout the world there are many minors who have no way to prove they are underaged, leading to a great interest in predicting legal age with the highest possible accuracy. Current methods, mainly involving X-ray analysis, are highly invasive, so new methods to predict legal age are being studied, such as DNA methylation. To further such studies, we created two age prediction models based on five epigenetic markers: cg21572722 (ELOVL2), cg02228185 (ASPA), cg06639320 (FHL2), cg19283806 (CCDC102B) and cg07082267 (no associated gene), that were analysed in blood samples to determine possible limitations regarding DNA methylation as an effective tool for legal age estimation. A wide age range prediction model was created using a broad set of samples (14–94 years) yielding a mean absolute error (MAE) of ±4.32 years. A second model, the constrained age prediction model, was created using a reduced range of samples (14–25 years) yielding an MAE of ±1.54 years. Both models, in addition to Horvath’s Skin & Blood epigenetic clock, were evaluated using a test set comprising 732 pairs of 18-year-old twins (N=426 monozygotic (MZ) and N=306 dizygotic (DZ) pairs), representing a relevant age of study. Through analysis of the two former age prediction models, we found that constraining the age of the samples forming the training set around the desired age of study significantly reduced the prediction error (from MAE: ±4.07 and ±4.27 years for MZ and DZ twins, respectively; to ±1.31 and ±1.3 years). However, despite low prediction errors, DNA methylation models are still prone to classify same-aged individuals in different categories (minors or adults), despite each sample belonging to the same twin pair. Additional evaluation of Horvath’s Skin & Blood model (391 CpGs) led to similar results in terms of age prediction errors than if using only five epigenetic markers (MAE: ±1.87 and ±1.99 years for MZ and DZ twins, respectively).
PB Elsevier
SN 1872-4973
YR 2024
FD 2024-07-27
LK https://hdl.handle.net/10347/39835
UL https://hdl.handle.net/10347/39835
LA eng
NO Boullón-Cassau, M., Ambroa-Conde, A., Casares de Cal, M. A., Gómez-Tato, A., Mosquera-Miguel, A., Ruiz-Ramírez, J., Cabrejas-Olalla, A., González-Bao, J., Casanova-Adán, L., de la Puente, M., Rodríguez, A., Phillips, C., Lareu, M., & Freire-Aradas, A. (2025). Exploring legal age estimation using DNA methylation. Forensic Science International: Genetics, 7410.1016/j.fsigen.2024.103142
NO MBC is supported by the "Programa de axudas á etapa predoutoral" funded by the Consellería de Cultura, Educación e Formación Profesional e Universitaria from Xunta de Galicia, Spain (ED481A-2024-163). JRR is supported by the “Programa de axudas á etapa predoutoral” funded by the Consellería de Cultura, Educación e Ordenación Universitaria e da Consellería de Economía, Emprego e Industria from Xunta de Galicia, Spain (ED481A-2020/039). JGB is supported by predoctoral grant “Ayudas para la Formación del Profesorado Universitario” (reference FPU22/02683) funded by Ministerio de Universidades from Gobierno de España. LCA is supported by a predoctoral grant funded by “Fundación Caixa Rural Galega Tomás Notario Vacas” in collaboration agreement with the Universidade de Santiago de Compostela. MdP is supported by grant IJC2020–042638-I funded by the Gobierno de España MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU/PRTR”. MVL is supported by grant PID2019–107876RB-I00 funded by the Ministerio de Educación, Cultura y Ciencia, Spain (MCIN/AEI/ 10.13039/501100011033) and grant PID2022–141224OB-I00 funded by MCIN/AEI/ 10.13039/501100011033 and “ERDF A way of making Europe”.
DS Minerva
RD 29 abr 2026