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Knowledge of these factors is of great relevance for the interpretation of DNA-methylation data for the estimation of chronological age in forensic casework. We performed a literature review to identify parameters, which might be of relevance for the prediction of chronological age based on DNA methylation. The quality of age predictions might particularly be influenced by lifetime adversities (chronic stress, trauma\/post-traumatic stress disorder (PTSD), violence, low socioeconomic status\/education), cancer, obesity and related diseases, infectious diseases (especially HIV and <jats:italic>Cytomegalovirus<\/jats:italic> (CMV) infections), sex, ethnicity and exposure to toxins (alcohol, smoking, air pollution, pesticides). Such factors may alter the DNA methylation pattern and may explain the partly high deviations between epigenetic age and chronological age in single cases (despite of low mean absolute deviations) that can also be observed with \u201cepigenetic clocks\u201d comprising a high number of CpG sites. So far, only few publications dealing with forensic age estimation address these confounding factors. Future research should focus on the identification of further relevant confounding factors and the development of models that are \u201crobust\u201d against the influence of such biological factors by systematic investigations under targeted inclusion of diverse and defined cohorts.<\/jats:p>","DOI":"10.1007\/s00414-020-02375-0","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:02:26Z","timestamp":1594684946000},"page":"2215-2228","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Epigenetic clocks may come out of rhythm\u2014implications for the estimation of chronological age in forensic casework"],"prefix":"10.1007","volume":"134","author":[{"given":"Barbara Elisabeth","family":"Koop","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Reckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Ritz-Timme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,14]]},"reference":[{"issue":"3","key":"2375_CR1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s004140050283","volume":"113","author":"S Ritz-Timme","year":"2000","unstructured":"Ritz-Timme S, Cattaneo C, Collins MJ, Waite ER, Schutz HW, Kaatsch HJ, Borrman HI (2000) Age estimation: the state of the art in relation to the specific demands of forensic practise. 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