title: Epigenetic age predictions based on buccal swabs are more precise in combination with cell type-specific DNA methylation signatures.
abstract: Aging is reflected by highly reproducible DNA methylation (DNAm) changes that open new perspectives for estimation of chronological age in legal medicine. DNA can be harvested non-invasively from cells at the inside of a person's cheek using buccal swabs - but these specimens resemble heterogeneous mixtures of buccal epithelial cells and leukocytes with different epigenetic makeup. In this study, we have trained an age predictor based on three age-associated CpG sites (associated with the genesPDE4C, ASPA, and ITGA2B) for swab samples to reach a mean absolute deviation (MAD) between predicted and chronological age of 4.3 years in a training set and of 7.03 years in a validation set. Subsequently, the composition of buccal epithelial cells versus leukocytes was estimated by two additional CpGs (associated with the genes CD6 and SERPINB5). Results of this "Buccal-Cell-Signature" correlated with cell counts in cytological stains (R2 = 0.94). Combination of cell type-specific and age-associated CpGs into one multivariate model enabled age predictions with MADs of 5.09 years and 5.12 years in two independent validation sets. Our results demonstrate that the cellular composition in buccal swab samples can be determined by DNAm at two cell type-specific CpGs to improve epigenetic age predictions.
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University, Aachen, Germany.|Institute for Biomedical Engineering - Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Eipel
authors.affiliation: Institute for Legal Medicine, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Mayer
authors.affiliation: Institute for Legal Medicine, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Arent
authors.affiliation: Department of Statistics, Centre for Natural and Exact Sciences, Federal University of Paraiba, 58051-900, João Pessoa, Brazil.|IZKF Computational Biology Research Group, University Hospital of RWTH Aachen, Aachen, Germany.
authors.forename: Marcelo R P
authors.initials: MR
authors.lastname: Ferreira
authors.affiliation: Varionostic GmbH, 89081 Ulm, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Birkhofer
authors.affiliation: Varionostic GmbH, 89081 Ulm, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Gerstenmaier
authors.affiliation: Institute for Biomedical Engineering - Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany.|IZKF Computational Biology Research Group, University Hospital of RWTH Aachen, Aachen, Germany.
authors.forename: Ivan G
authors.initials: IG
authors.lastname: Costa
authors.affiliation: Institute for Legal Medicine, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ritz-Timme
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University, Aachen, Germany.|Institute for Biomedical Engineering - Cell Biology, University Hospital of RWTH Aachen, Aachen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000581:Amidohydrolases / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000235:genetics; D004247:DNA / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007223:Infant; D039421:Integrin alpha2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: C056564:ITGA2B protein, human; D039421:Integrin alpha2; D004247:DNA; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517361:PDE4C protein, human; D000581:Amidohydrolases; C019751:aspartoacylase
keywords: aging; cell composition; epigenetic; epithelial cells; methylation; predictor; swab