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Obesity is also reflected in the genome


The holiday pounds are not only deposited on the hips, but also on the DNA. This is the result of a large international study led by the Helmholtz Zentrum München, partner in the German Center for Diabetes Research, which has now been published in 'Nature'. It shows that an increased BMI leads to epigenetic changes in almost 200 parts of the genome - with effects on the genes.

While our genes hardly change in the course of life, our lifestyle can have a direct influence on their environment. Scientists speak of the epigenome (Greek epi: on, on, at), i.e. everything that happens on and around the genes. So far it has hardly been investigated how the epigenome changes due to obesity. "The question is quite relevant for an estimated one and a half billion overweight people worldwide," said the first author of the study Dr. Simone Wahl from the Department of Molecular Epidemiology (AME) at the Helmholtz Zentrum München. "Especially when you know that being overweight can lead to complications such as diabetes, cardiovascular and metabolic diseases."

World's largest study on BMI and epigenetics
The international team of researchers led by Dr. Christian Gieger and Dr. Harald Grallert from AME (as well as Jaspal Kooner and John Chambers from Imperial College London) therefore examined possible correlations between the Body Mass Index (BMI) and epigenetic changes *. With the ever-improving technological possibilities, they implemented the world's largest study on this subject.

To this end, the scientists examined the blood samples from over 10,000 women and men from Europe. A large proportion of them were residents of London of Indian origin, who, according to the authors, are at high risk of obesity and metabolic diseases. In a first step with 5,387 samples **, the research team identified 207 gene locations that were epigenetically changed depending on the BMI. They then tested these candidates on blood samples from a further 4,874 subjects and were able to confirm 187 of them ***. Further examinations and long-term observations also indicated that a large part of the changes were a result of the overweight and not its cause.

Significant changes also in inflammatory genes
"Significant changes occurred primarily in genes that are responsible for fat metabolism and mass transport, but also inflammation genes were affected," explains group leader Harald Grallert. The team was also able to use the data to identify epigenetic markers that could be used to predict the risk of type 2 diabetes.

"Our results provide new insights into which signaling pathways are affected by obesity," said Christian Gieger, head of AME. "We hope that this will give rise to new strategies on how to predict and, at best, prevent type 2 diabetes and other consequences of being overweight." In the future, the researchers also want to investigate the epigenetic effects of translational research at the German Center for Diabetes Research Changes in detail affect the activity of the underlying genes.

Further information
* Specifically, the team examined the methylation pattern, i.e. the presence or absence of methyl groups on the DNA. These methylation patterns can now be examined relatively quickly and on a large scale using so-called high-throughput measurements.

** Among others from the Augsburg KORA study, the London LOLIPOP study and part of the EPICOR study from Italy

*** Some of them were subsequently also confirmed in adipose tissue, which showed that changes in gene regulation in disease-relevant tissues are also visible in the blood.

Original publication:
Wahl, S. et al. (2016): Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity. Nature, doi: 10.1038 / nature20784

Author and source information



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