Intra-individual Change Over Time in DNA Methylation With Familial Clustering
Open accessAbstract
CONTEXT: Changes over time in epigenetic marks, which are modifications of DNA such as by DNA methylation, may help explain the late onset of common human diseases. However, changes in methylation or other epigenetic marks over time in a given individual have not yet been investigated. OBJECTIVES: To determine whether there are longitudinal changes in global DNA methylation in individuals and to evaluate whether methylation maintenance demonstrates familial clustering. DESIGN, SETTING, AND PARTICIPANTS: We measured global DNA methylation by luminometric methylation assay, a quantitative measurement of genome-wide DNA methylation, on DNA sampled at 2 visits on average 11 years apart in 111 individuals from an Icelandic cohort (1991 and 2002-2005) and on average 16 years apart in 126 individuals from a Utah sample (1982-1985 and 1997-2005). MAIN OUTCOME MEASURE: Global methylation changes over time. RESULTS: Twenty-nine percent of Icelandic individuals showed greater than 10% methylation change over time (P < .001). The family-based Utah sample also showed intra-individual changes over time, and further demonstrated familial clustering of methylation change (P = .003). The family showing the greatest global methylation loss also demonstrated the greatest loss of gene-specific methylation by a separate methylation assay. CONCLUSION: These data indicate that methylation changes over time and suggest that methylation maintenance may be under genetic control.
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Dynamic changes in DNA methylation occur across tissues during aging in humans, nonhuman primates, and mice.
“it is shown that dynamic changes in DNA methylation occur across tissues during aging in humans10, nonhuman primates11, and mice12,13.”
From Integrated analysis of behavioral, epigenetic, and gut microbiome analyses in AppNL-G-F, AppNL-F, and wild type mice (2021) · cites this paper as [10]
The Results report DNA methylation changes over time within individuals in two human cohorts. They identify lymphocytes as the cell type studied and only suggest that lymphoid tissue might reflect changes in other tissues; this source does not establish changes across tissues. The nonhuman-primate and mouse portions of the sentence have separate citations. (LLM, conf=0.86)
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- Authors
- Bjornsson, H. T.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Bjornsson, Hans T.
- ORCID
- Bjornsson, Hans T.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2008-06-25
- Volume
- 299
- Issue
- 24
- Pages
- 2877
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC2581898
- OpenAlex
- W2130189740
- Cited by
- 702
- References
- 2
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 11 · 2023: 30 · 2022: 20 · 2021: 45 · 2020: 23 · 2019: 26 · 2018: 27 · 2017: 36 · 2016: 29 · 2015: 56 · 2014: 56 · 2013: 57 · 2012: 87
- FWCI
- 24.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Funders
- W. M. Keck Foundation
- Swedish Cancer Foundation
- National Institutes of Health (n01ag12100-57-0-2, N01-AG-1-2100, M01-RR00064)
- National Institute on Aging (N01-AG012100, Z01AG007380)
- National Human Genome Research Institute (P50HG003233)
- National Institute of General Medical Sciences (R01GM083084)
- National Institute of Environmental Health Sciences (R01ES015211)
- National Center for Research Resources (R01RR021967, M01-RR 00064, M01RR000064)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- DNA methylation, longitudinal change, within-person variability, familial aggregation, epigenetics, gene-specific methylation, late-onset disease, global DNA methylation
- MeSH terms
- Aged, Aged, 80 and over, Female, Humans, Iceland, Longitudinal Studies, Luminescent Measurements, Male, Pedigree, Time Factors, Utah, DNA Methylation, Epigenesis, Genetic
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