Changes of epigenetic marks over time may help explain the late onset of common human disease.
To determine whether there are longitudinal changes of global DNA methylation in individuals, and to evaluate whether methylation maintenance demonstrates familial clustering.
Design, Setting and Participants
Changes in HpaII methylation over time in a given individual have not yet been investigated. Here we measured global DNA methylation quantitatively by LUminometric Methylation Assay (LUMA), a quantitative measurement of genome-wide DNA methylation, on DNA sampled at two visits on average 11 years apart in an Icelandic cohort (1991 and 2002-2005) and on average 16 years apart in a Utah sample (1982-1985 and 1997-2005).
Main Outcome Measure
Global methylation changes over time.
Twenty-nine percent of Icelandic individuals showed >10% methylation change over time (p<0.0001). The family-based Utah sample also showed intra-individual changes over time, and further demonstrated familial clustering of methylation change (p=0.003). The family showing greatest global methylation loss also demonstrated the greatest loss of gene-specific methylation by a separate methylation assay.
These data indicate that methylation does change over time and suggest that methylation maintenance may itself be under genetic control.
Epigenetic marks are modifications of DNA or associated proteins, other than the DNA sequence, that are heritable during cell division. Since the DNA remains the same, but epigenetic marks change over one’s lifetime, changes of epigenetic marks over time may help explain the late onset of common human disease. Here we determined whether there are longitudinal changes of global DNA methylation in individuals, and evaluated whether methylation maintenance demonstrates familial clustering. We examined an Icelandic cohort sampled at two visits 11 years apart on average, and found that 29% changed >10% in their DNA methylation level. A second Utah cohort sampled at two visits 16 years apart on average showwed similar changes over time, with familial clustering. Thus, DNA be under genetic control.