Epigenetic age predictions based on buccal swabs are more precise in combination with cell type-specific DNA methylation signatures

被引：2

作者：

Eipel, Monika ^{[1
,2
]}

Mayer, Felix ^{[3
]}

Arent, Tanja ^{[3
]}

Ferreira, Marcelo R. P. ^{[4
,5
]}

Birkhofer, Carina ^{[6
]}

Gerstenmaier, Uwe ^{[6
]}

Costa, Ivan G. ^{[2
,5
]}

Ritz-Timme, Stefanie ^{[3
]}

Wagner, Wolfgang ^{[1
,2
]}

机构：

[1] Rhein Westfal TH Aachen, Helmholtz Inst Biomed Engn Stem Cell Biol & Cellu, Aachen, Germany

[2] Univ Hosp RWTH Aachen, Inst Biomed Engn Cell Biol, Aachen, Germany

[3] Univ Dusseldorf, Inst Legal Med, Dusseldorf, Germany

[4] Univ Fed Paraiba, Ctr Nat & Exact Sci, Dept Stat, BR-58051900 Joao Pessoa, Paraiba, Brazil

[5] Univ Hosp RWTH Aachen, IZKF Computat Biol Res Grp, Aachen, Germany

[6] Varionostic GmbH, D-89081 Ulm, Germany

来源：

AGING-US | 2016年 / 8卷 / 05期

关键词：

aging; predictor; epigenetic; methylation; swab; cell composition; epithelial cells; BLOOD; SMOKING; CANCER; LOCI; CLASSIFICATION; ASSOCIATION; MORTALITY; GENDER; MARKER; LIFE;

D O I：

暂无

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 genes PDE4C, 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 (R-2 = 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.

引用

页码：1034 / 1048

页数：15

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