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Epigenetic differences arise during the lifetime of monozygotic twins
Open accessAbstract
Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait. These findings indicate how an appreciation of epigenetics is missing from our understanding of how different phenotypes can be originated from the same genotype.
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“genetics alone do not account for most of the risk of major depression.”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [17]
Experimental — accuracy not yet measuredIn the citing paper
“Environmental conditions clearly influence epigenetic profiles in human immune cells [37], and some studies have begun to link immune cell DNA methylation profiles to specific social environmental conditions such as low social status [7] and early life stress exposure [38]–[41].”
From Human Social Genomics (2014) · cites this paper as [37]
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“Identical twin studies have shown a high discordance rate for MDD of 50%, indicating the importance of non-genetic factors.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [4]
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“Studies with monozygotic twins suggest the accumulation of epigenetic changes as twins age (e.g., demethylation of 5-methylcytosines in DNA), thus affecting the transcriptome (Fraga et al., 2005).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Fraga et al., 2005
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“For example, identical twins diverge over the life course in patterns of CpG methylation of their DNA reflecting the influence of “non-shared” experiences.”
From Neurobiological and Systemic Effects of Chronic Stress (2017) · cites this paper as [76]
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Metadata
- Authors
- Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suñer, D., Cigudosa, J. C., Urioste, M., Benitez, J., Boix-Chornet, M., Sanchez-Aguilera, A., Ling, C., Carlsson, E., Poulsen, P., Vaag, A., Stephan, Z., Spector, T. D., Wu, Y.-Z., Plass, C., & Esteller, M.
- Affiliations
- Universitat de València (ES)
- Epigenetics, Cytogenetics, and Genetic Laboratories, Spanish National Cancer Centre (CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain; Department of Behavioral Science, University of Valencia, 46010 Valencia, Spain; Molecular Genetics Laboratory, Genetics Department, Son Dureta Hospital, 07014 Palma de Mallorca, Spain; Department of Clinical Sciences, University Hospital Malmö, Lund University, S-205 02 Malmö, Sweden; Steno Diabetes Center, 2820 Gentofte, Denmark; Twin Research and Genetic...
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-07-11
- Volume
- 102
- Issue
- 30
- Pages
- 10604-10609
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1174919
- OpenAlex
- W2134555277
- Cited by
- 3,602
- References
- 20
- Citations by year
- 2026: 65 · 2025: 87 · 2024: 113 · 2023: 115 · 2022: 143 · 2021: 119 · 2020: 147 · 2019: 161 · 2018: 185 · 2017: 173 · 2016: 191 · 2015: 225 · 2014: 223 · 2013: 242 · 2012: 293
- FWCI
- 51.76
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
- Hispana (submittedVersion)
- Docusalut (Conselleria de Salut i Consum del Govern de les Illes Balears) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- 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 › Assisted Reproductive Technology and Twin Pregnancy
- Keywords
- monozygotic twins, epigenetic variation, DNA methylation, histone acetylation, 5-methylcytosine, phenotypic discordance, gene expression, aging
- MeSH terms
- Acetylation, Adult, Analysis of Variance, Female, Histones, Humans, Male, Phenotype, Surveys and Questionnaires, Spain, Twins, Monozygotic, Restriction Mapping, Sequence Analysis, DNA, Gene Expression Regulation, Developmental, Electrophoresis, Capillary, DNA Methylation, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Nucleic Acid Amplification Techniques, Epigenesis, Genetic, 5-Methylcytosine, X Chromosome Inactivation
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