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@ARTICLE{Mayer:907806,
author = {Mayer, F. and Becker, J. and Reinauer, C. and Böhme, P.
and Eickhoff, S. B. and Koop, B. and Gündüz, T. and Blum,
J. and Wagner, W. and Ritz-Timme, S.},
title = {{A}ltered {DNA} methylation at age-associated {C}p{G} sites
in children with growth disorders: impact on age
estimation?},
journal = {International journal of legal medicine},
volume = {136},
number = {4},
issn = {0044-3433},
address = {Heidelberg},
publisher = {Springer},
reportid = {FZJ-2022-02225},
pages = {987-996},
year = {2022},
abstract = {Age estimation based on DNA methylation (DNAm) can be
applied to children, adolescents and adults, but many CG
dinucleotides (CpGs) exhibit different kinetics of
age-associated DNAm across these age ranges. Furthermore, it
is still unclear how growth disorders impact epigenetic age
predictions, and this may be particularly relevant for a
forensic application. In this study, we analyzed buccal
mucosa samples from 95 healthy children and 104 children
with different growth disorders. DNAm was analysed by
pyrosequencing for 22 CpGs in the genes PDE4C, ELOVL2, RPA2,
EDARADD and DDO. The relationship between DNAm and age in
healthy children was tested by Spearman's rank correlation.
Differences in DNAm between the groups "healthy children"
and the (sub-)groups of children with growth disorders were
tested by ANCOVA. Models for age estimation were trained (1)
based on the data from 11 CpGs with a close correlation
between DNAm and age (R ≥ 0.75) and (2) on five CpGs that
also did not present significant differences in DNAm between
healthy and diseased children. Statistical analysis revealed
significant differences between the healthy group and the
group with growth disorders (11 CpGs), the subgroup with a
short stature (12 CpGs) and the non-short stature subgroup
(three CpGs). The results are in line with the assumption of
an epigenetic regulation of height-influencing genes. Age
predictors trained on 11 CpGs with high correlations between
DNAm and age revealed higher mean absolute errors (MAEs) in
the group of growth disorders (mean MAE 2.21 years versus
MAE 1.79 in the healthy group) as well as in the short
stature (sub-)groups; furthermore, there was a clear
tendency for overestimation of ages in all growth disorder
groups (mean age deviations: total growth disorder group
1.85 years, short stature group 1.99 years). Age estimates
on samples from children with growth disorders were more
precise when using a model containing only the five CpGs
that did not present significant differences in DNAm between
healthy and diseased children (mean age deviations: total
growth disorder group 1.45 years, short stature group 1.66
years). The results suggest that CpGs in genes involved in
processes relevant for growth and development should be
avoided in age prediction models for children since they may
be sensitive for alterations in the DNAm pattern in cases of
growth disorders.},
cin = {INM-7},
ddc = {610},
cid = {I:(DE-Juel1)INM-7-20090406},
pnm = {5251 - Multilevel Brain Organization and Variability
(POF4-525)},
pid = {G:(DE-HGF)POF4-5251},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35551445},
UT = {WOS:000799080600001},
doi = {10.1007/s00414-022-02826-w},
url = {https://juser.fz-juelich.de/record/907806},
}