Epigenetic studies using twins offer the advantage of allowing both a better understanding of the factors regulating epigenetic profiles, and of the role that epigenetic effects have in common diseases and complex traits.

Since monozygotic (MZ) twins are genetically identical while dizygotic (DZ) twins share 50% of their polymorphic SNPs, within-pair comparisons of MZ twins rule out the confounding by genetics and shared environment, while comparing MZ vs DZ twins allow the estimation of the proportion of the variance in epigenetic marks, or traits, explained by genotype and shared and non-shared environments. These study designs have proven incredibly valuable in studying the complexity of gene-environment-epigenetic interactions contributing to human health and disease.

Research strategies

Investigation of epigenetic marks in complex diseases and traits using discordant MZ twin pair study design

The functional genotype of MZ co-twins diverges over time as epigenetic and various environmental effects modify gene expression. At the same time the genomic DNA sequence remains unchanged, except for possible somatic mutations. Here we aim to pinpoint tissue specific epigenetic changes associated with various traits by studying DNA methylation, histone modifications and microRNA in genome scale in trait discordant MZ twin pairs.

Assessing genetic and epigenetic alterations and their interaction with pertinent environmental or lifestyle exposures to obtain more precise estimates of their individual and joint effects on common disease progression and risk

We combine the data on genetic and epigenetic alterations and assess their interaction with pertinent environmental/lifestyle exposures to obtain more precise estimates of their individual and joint effects on common disease progression and risk. Here we overlay epigenotype and genotype data, as well as other large scale datasets to perform thorough epidemiological analyses in various complex traits.

Epigenome as a biomarker

As the epigenome reacts to environmental effects, it may serve as a reliable biomarker. We use DNA methylation as a marker for biological aging, and assess its relationship to various complex traits, such as physical activity and obesity. We also use DNA methylation as a reliable indicator of smoking status. As it has been shown that smoking causes both stable and reversible methylation alterations, we have used this property of DNA methylation and built an EpiSmokEr tool which estimates the smoking status of an individual from any DNA sample.