Why Do Identical Twins Have Different Molecular Marks? A New Look at Gene – Environment Interactions

20th February 2026 – by TwinsUK

Summary of Key Findings

Even though identical twins share the same DNA sequence, they often grow up to have different health journeys. To help understand why and how this can happen, we have been studying a group of molecular pathways, called epigenetic signals. Our latest research, published in Genome Biology, looked at one epigenetic mechanism – DNA methylation – a “dimmer switch” through which our genes can be turned up or down by our genetics and environment. We found that these methylation “switches” can be set at very different levels in twins.

To understand why, we looked at Gene-Environment (GxE) interactions. The idea is that people of different genetic backgrounds show varied sensitivity to environmental changes. For example, twins of a certain genotype may have high molecular sensitivity to smoking – in this case if one twin in a pair smokes and the other does not, we would see big differences in DNA methylation between the two twins. Conversely, another genotype might show much lower molecular sensitivity to smoking, meaning that the twins would show very little difference in their methylation levels regardless of whether or not they smoke.

We discovered over 300 specific positions in the genome, which we call variance-methylation Quantitative Trait Loci (vmeQTLs), that help us identify these regions of molecular sensitivity to environmental factors. While the majority of these differences arise from different types of cells in our blood, some signals reflect how smoking and obesity interact with our genetics to affect the function of our genes. We found that these signals are robust in different twin cohorts, over time, and even in non-twins, proving they are a reliable way to study the GxE interactions.

Why matters for TwinsUK participants?

This research helps us to answer the question: “Why do monozygotic twins respond differently to the same environment?” by identifying regions in our genome that respond differently at a molecular level – to environmental changes.

By identifying these genomic regions, we can tell that some people are genetically more responsive to some environmental changes than others. In the long run, this can help us move toward personalised health advice, for example, by identifying which people are more likely to show a molecular response to a lifestyle intervention. Instead of “one size fits all” medical tips, we can eventually understand how one’s specific genetic makeup responds to their specific environment.

Every sample and data point helps us bridge the gap between our genetics and our health. We couldn’t map this complex landscape without the incredible commitment of the twin community.