DNA methylation profiles in monozygotic and dizygotic twins

Kaminsky, Zachary; Tang, Thomas S. Y.; Wang, Sun Chong; Ptak, Carolyn; Oh, Gabriel; Wong, Albert H.C.; Feldcamp, Laura; Virtanen, Carl; Halfvarson, Jonas; Tysk, Curt; McRae, Allan F.; Visscher, Peter M.; Montgomery, Grant W.; Gottesman, Irving I.; Martin, Nicholas G.; Petronis, Art

doi:10.1038/ng.286

Cited by 626 publications

(482 citation statements)

References 27 publications

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“…Microarray studies confirmed a decrease in DNA methylation with age, while site‐specific analysis indicated an increase in variability of DNA methylation with age. The latter was first noted in monozygotic twins, and subsequently in unrelated individuals (Fraga et al ., 2005; Martin, 2005; Poulsen et al ., 2007; Kaminsky et al ., 2009; Martino et al ., 2011). These studies also supported the idea that DNA methylation showed reduced stringency in maintenance over the lifespan, resulting in an increase in interindividual variability along with the overall decrease in DNA methylation.…”

Section: Dna Methylation Dynamics During Agingmentioning

confidence: 99%

“…Epigenetic drift is now understood to comprise age‐related changes in the epigenome that include those that are acquired environmentally as well as stochastically (Fraga et al ., 2005; Fraga & Esteller, 2007; Kaminsky et al ., 2009; Hannum et al ., 2013; Teschendorff et al ., 2013). Early indications of epigenetic drift were noted in cell culture studies, after the observation that clones of a single cell line became epigenetically divergent upon multiple passages (Humpherys et al ., 2001).…”

Section: Epigenetic Drift Vs the Epigenetic Clock: Two Phenomena Undmentioning

confidence: 99%

“…Similar studies in adults have shown greater concordance in DNA methylation profiles between monozygotic twins than dizygotic twins (Kaminsky et al ., 2009; Bell et al ., 2011). One study examined twins to determine the heritability of discordance between epigenetic and chronological age and determined that at birth, the heritability is 100% but drops to 39% in adulthood (Horvath, 2013).…”

Section: Considerations For Studies Of Epigenetics and Agingmentioning

confidence: 99%

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DNA methylation and healthy human aging

2015

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SummaryThe process of aging results in a host of changes at the cellular and molecular levels, which include senescence, telomere shortening, and changes in gene expression. Epigenetic patterns also change over the lifespan, suggesting that epigenetic changes may constitute an important component of the aging process. The epigenetic mark that has been most highly studied is DNA methylation, the presence of methyl groups at CpG dinucleotides. These dinucleotides are often located near gene promoters and associate with gene expression levels. Early studies indicated that global levels of DNA methylation increase over the first few years of life and then decrease beginning in late adulthood. Recently, with the advent of microarray and next‐generation sequencing technologies, increases in variability of DNA methylation with age have been observed, and a number of site‐specific patterns have been identified. It has also been shown that certain CpG sites are highly associated with age, to the extent that prediction models using a small number of these sites can accurately predict the chronological age of the donor. Together, these observations point to the existence of two phenomena that both contribute to age‐related DNA methylation changes: epigenetic drift and the epigenetic clock. In this review, we focus on healthy human aging throughout the lifetime and discuss the dynamics of DNA methylation as well as how interactions between the genome, environment, and the epigenome influence aging rates. We also discuss the impact of determining ‘epigenetic age’ for human health and outline some important caveats to existing and future studies.

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Section: Dna Methylation Dynamics During Agingmentioning

confidence: 99%

Section: Epigenetic Drift Vs the Epigenetic Clock: Two Phenomena Undmentioning

confidence: 99%

Section: Considerations For Studies Of Epigenetics and Agingmentioning

confidence: 99%

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DNA methylation and healthy human aging

2015

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“…In addition, it has been suggested that age-related methylation alterations depend on genetic effects [9], and another recent study on mother-children pairs reported that meQTL associations were stable over time [12]. Twin studies of the epigenome have been used to estimate methylation heritability [9,13], and higher methylation correlation has been observed in monozygotic (MZ) than dizygotic (DZ) twin pairs [5,14]. However, the change of intra-twin-pair methylation difference over time has not been studied.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins

et al. 2018

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Age-related changes in DNA methylation were observed in cross-sectional studies, but longitudinal evidence is still limited. Here, we aimed to characterize longitudinal age-related methylation patterns using 1011 blood samples collected from 385 Swedish twins (age at entry: mean 69 and standard deviation 9.7, 73 monozygotic and 96 dizygotic pairs) up to five times (mean 2.6) over 20 years (mean 8.7). We identified 1316 age-associated methylation sites (P<1.3×10−7) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, 390 samples) (P<3.9×10−5), 594 in Lothian Birth Cohort (LBC, 3018 samples) (P<5.1×10−5) and 63 in both. Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other transcription factor binding sites. We further investigated genetic influences on methylation and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased with 6.4% over 10 years, where monozygotic twins had smaller intra-pair differences than dizygotic twins. In conclusion, we show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. The changes are under genetic influence, although this effect is independent of age. Moreover, methylation variability increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.

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“…Kaminsky et al mapped differences in DNA methylation at a locus displaying a range of co-twin variability in three types of tissues-white blood cells, buccal epithelial cells, gut (rectum) biopsies and-from MZ and DZ twin pairs using microarrays [Schumacher et al, 2006]. They found a large degree of MZ co-twin DNA methylation variation in all the tissue samples investigated, validating their findings using sodium bisulfite modification based mapping of methylated cytosines in CpG islands [Frommer et al, 1992;Kaminsky et al, 2009]. There are a number of specific epigenetic mechanisms that may alter phenotype, including skewed X-inactivation in FMZ twins, imprinting (differential expression of genes inherited from the mother or father), and DNA methylation, that are discussed below [Gringras and Chen, 2001;Boomsma et al, 2002;Rosa et al, 2008].…”

Section: New Directions In Twin Studies: Epigeneticsmentioning

confidence: 83%

Not really identical: Epigenetic differences in monozygotic twins and implications for twin studies in psychiatry

Haque

Gottesman

Wong

2009

American J of Med Genetics Pt C

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Classical twin studies in the field of psychiatry generally fall into one of two categories: (1) those designed to identify environmental risk factors causing discordance in monozygotic (MZ) twins and (2) those geared towards identifying genetic risk factors. However, neither environment nor differences in DNA sequence can fully account for phenotypic discordance among MZ twins. The field of epigenetics -DNA modifications that can affect gene expression -offers new models to understand discordance in MZ twins. In the past, MZ twins were regarded as genetically-identical controls for differing environmental conditions. In contrast, the evolving current concept is that epigenetic differences between MZ twins may modulate differences in diverse phenotype, from disease to personality. In this article, we review some twin studies, and discuss the dynamic interactions between stochastic, environmental, and epigenetic variables that influence neurobiological phenotypes. ß

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DNA methylation profiles in monozygotic and dizygotic twins

Cited by 626 publications

References 27 publications

DNA methylation and healthy human aging

DNA methylation and healthy human aging

Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins

Not really identical: Epigenetic differences in monozygotic twins and implications for twin studies in psychiatry

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