From stem cells to the law courts: DNA methylation, the forensic epigenome and the possibility of a biosocial archive.

The growth in epigenetics continues to attract considerable cross-disciplinary interest, apparently representing an opportunity to move beyond genomics towards the goal of understanding phenotypic variability from molecular through organismal to the societal level. The epigenome may also harbour useful information about lifetime exposures (measured or unmeasured) irrespective of their influence on health or disease, creating the potential for a person-specific biosocial archive. Furthermore, such data may prove of use in providing identifying information, providing the possibility of a future forensic epigenome. The mechanisms involved in ensuring that environmentally induced epigenetic changes perpetuate across the life course remain unclear. Here we propose that a potential role of adult stem cells in maintaining epigenetic states provides a useful basis for formulating such epidemiologically-relevant concepts. Epigenetics encompasses different mechanisms of gene expression regulation, the most commonly discussed ones being DNA methylation, histone modifications and non-coding RNAs. 1,2 The epigenetic mechanism most studied to date is DNA methylation—addition of a methyl group (CH 3) at the 5' position of a cytosine base, typically at CpG dinucleotides which are often clustered in CpG-rich DNA segments called CpG islands. 3,4 This chemical addition is made by a covalent bond and is stable over time. Since epigenetic processes are believed to be modifiable by environmental (i.e. non-genetic) factors, much of the current interest in epigenetics lies in understanding how the environment influences gene expression—even though, as currently analysable, epigenetics is unlikely to hold all of the answers for this broad and rather complex question. 2,5 Technological advances now allow epige-nome-wide investigations to be performed in large human populations at affordable costs—especially with respect to DNA methylation. 6,7 Although other measures are technically possible, they remain prohibitively expensive on a population scale. Epidemiological studies involving DNA methylation pertain to one of the most recent branches of epidemiology—epigenetic epidemiology. 8 Large-scale profiling of DNA methylation levels has been applied to case-control studies, 9,10 densely-phenotyped cohorts 11 and in some instances serial samples from the same longitudinal cohort. 12 This allows investigation of the determinants of variation in DNA methylation and their importance in the context of different health outcomes and traits, as evidenced by the steady rise in epigenetic epidemiology publications (Figure 1) and the numerous studies reported in this issue of the IJE. Methylation modifications are relatively stable. Indeed, such stability is important in the maintenance of methyla-tion modifications that regulate developmental processes, such as cell differentiation. 25–28 …