DNA methylation studies using twins: what are they telling us?

Abstract

Recent studies have identified both heritable DNA methylation effects and differential methylation in disease-discordant identical twins. Larger sample sizes, replication, genetic-epigenetic analyses and longitudinal assays are now needed to establish the role of epigenetic variants in disease.

Familial resemblances in blood leukocyte DNA methylation levels

“…9 Finally, DNA methylation is specific to the type of cell, tissue, locus, and developmental stages, which affects DNA methylation heritability estimates. 13 However, McRae et al reported little effect of the cellular composition of blood samples on the heritability estimates for the majority of probes (genetic heritability reduced from 19.9% to 17.6%). 9 Other studies have also reported that DNA methylation patterns are globally correlated between 11 different somatic tissues.…”

“…9,16 Transgenerational similarity in DNA methylation levels has also been reported. 13 Several genome-wide association studies with methylation quantitative trait loci (mQTL) in both cis and trans locations have confirmed the genetic heritability of DNA methylation. 14,17,18 However, it is difficult to understand to what extent the observed familial resemblance in DNA methylation is due to genetic heritability and/or common environmental effect.…”

“…12 Studies with twins have also demonstrated a greater similarity in DNA methylation levels in monozygotic twins compared to dizygotic twins. 13 Twin studies also reported an average estimated genetic heritability of DNA methylation (proportion of variance explained by additive genetic factors) between 12 and 18% in whole blood, 14,15 5% in placenta, 15 and 7% in human umbilical vascular endothelial cells. 15 These studies using promoter-specific genome-wide DNA methylation array (Illumina 27K) examined only a fraction of methylation variations.…”

Aging-related magnification of genetic effects on cognitive and brain integrity

“…Note, however, that gene-environment interactions might occur without any epigenetic modification. Moreover, individual differences in epigenetic mechanisms may also be inherited [90]. Therefore, it is vital to show longitudinally that lifestyle changes or interventions directly affect expression of a particular gene through epigenetic mechanisms, and consequently brain and cognition.…”

Establishing a Twin Register: An Invaluable Resource for (Behavior) Genetic, Epidemiological, Biomarker, and ‘Omics’ Studies

“…These data are important to understand the nature of genetic variance components as established in twin and family studies (Schadt et al, 2005), and are themselves subject to such studies, for example, studies of the heritability of methylation and gene expression (Bell & Spector, 2012;McRae et al, 2014; Petronis,…”