The IIEG was involved in one of the largest epigenome-wide association studies (EWAS) of its kind, in which we have identified a new genetic mechanism that may play a role in mediating some of the harmful effects of becoming overweight, such as diabetes.
In this study, published in The Lancet, Samani and colleagues looked at epigenetic changes in DNA in relation to body mass index (BMI), a widely used measure of obesity. One particular type of epigenetic change, a process known as DNA methylation, was examined. DNA methylation involves specific locations along the DNA called cytosine bases being modified through the addition of methyl chemical groups.
We used microarray technology to measure methylation levels at over 351 000 sites across the genome using whole blood DNA samples taken from 459 individuals of European origin, and identified five sites where the level of methylation correlated with BMI.
We found that for every 10% increase in methylation at the most significant site—cg22891070—BMI increased by 3·6%, equating to about 0·98 kg/m2 for a person in the original cohort with an average BMI of 27 kg/m2. In comparison, the obesity risk gene, FTO, accounts for a more modest 0.39kg/ m2 increase in BMI.
However, further studies are needed to understand how and when obesity affects methylation at HIF3A and what the consequences are, but the findings could eventually lead to new treatments that may tackle the adverse effects of obesity on health.
At a more general level, our study shows that investigating epigenetic changes in DNA may reveal new mechanisms involved in common diseases.