New research reveals how genes shape responses to the environment
12th March 2026 – By King’s College London
Researchers at King’s College London have used a study of identical twins to uncover how genetic differences influence the way our bodies respond to environmental factors such as obesity and smoking.
The research, published in Genome Biology, set out to identify gene–environment interactions that influence human traits and, ultimately, disease risk. While many genetic studies focus on variations in DNA that affect human characteristics, this research instead examined how genes influence variation in DNA methylation – a key process that controls how much genes are turned on or off.
To do this, the researchers analysed data from nearly 1,000 pairs of identical twins from the TwinsUK cohort and the Netherlands Twin Register. Identical twins share the same DNA, but can have very different levels of DNA methylation, and these methylation differences can reflect different sensitivity to environment changes. This study design allowed the researchers to look at how genetic and environmental effects interact.
By comparing methylation differences within each twin pair, the researchers identified genetic variants that influence how sensitive DNA methylation is to environmental exposures. Using a two-stage approach, they first identified variants where twins with certain genetic backgrounds were more different from each other than others, signalling potential gene–environment interactions. They then tested these variants for interactions with specific environmental factors.
The researchers examined interactions with smoking, obesity and blood cell composition. They identified over 300 genetic variants that influence DNA methylation variability, many of which showed consistent gene–environment effects across both twin cohorts. Several of these findings were also confirmed in non-twin populations and remained stable over time.
Professor Jordana Bell, Professor of Epigenetics at King’s and senior author of the study, said:
“Most human traits and diseases are influenced by both genetics and environment, but capturing how these two factors interact can be very challenging. Here, by using genetically identical twins, we’re able to generate replicable evidence of gene–environment interactions.”
The findings from this research suggest that some individuals could be more biologically sensitive to environmental stressors. For example, at the same level of obesity, some people may show stronger methylation changes linked to metabolic health risk, while others appear more resilient.
This could help guide personalised lifestyle or healthcare interventions, by showing who may be more or less responsive to changes such as diet and exercise.
Xiaopu Zhang, PhD student at King’s and first author of the paper, said:
“Understanding gene–environment interactions may allow us to better stratify and prioritise individuals for interventions. It’s not about predicting who will get a disease, but about identifying who could benefit most from certain interventions or healthy habits.”
The researchers are now extending this work into larger population studies to further explore how genetic sensitivity to environmental exposures shapes human health.