Obesity is also reflected in the genetic material

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 increased BMI leads to epigenetic changes in nearly 200 sites of the genome - with effects on genes.

While our genes hardly change over the course of life, our lifestyle can have a direct impact on their environment. Scientists speak here of the epigenome (Greek epi: on, on, bei), ie 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 estimated to be relevant in an estimated one and a half billion overweight people worldwide," said the first author of the study. Simone Wahl of the Department of Molecular Epidemiology (AME) at Helmholtz Zentrum München. "Especially when you know that overweight can lead to sequelae such as diabetes, cardiovascular and metabolic diseases."

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World's largest study on BMI and epigenetics
The international research team led by Dr. med. Christian Gieger and dr. Harald Grallert from the AME (as well as Jaspal Kooner and John Chambers from Imperial College London) therefore examined possible connections between the body mass index (BMI) and epigenetic changes *. With the ever-improving technological possibilities, they realized the largest study to date on this topic to date.

The scientists examined the blood samples of over 10,000 women and men from Europe. A larger proportion of them were residents of London of Indian descent who, according to the authors, are at high risk for obesity and metabolic diseases. In a first step with 5,387 samples **, the research team identified 207 gene loci that were epigenetically altered, depending on the BMI. These candidates then tested them for blood samples from a further 4,874 subjects and confirmed 187 of them ***. Further investigation and long-term observations also indicated that much of the change was due to overweight and not its cause.

Significant changes also to inflammatory genes
"Significant changes were mainly to genes that are responsible for the fat metabolism and mass transport, but also inflammation genes were affected," explains group leader Harald Grallert. Furthermore, the team identified epigenetic markers from the data to predict the risk of type 2 diabetes.

"Our results allow new insights into which signaling pathways are affected by obesity," said Christian Gieger, director of AME. "We hope that this will lead to new strategies for predicting and at best preventing type 2 diabetes and other consequences of obesity." In the future, the researchers also want to investigate how the epigenetic epidemiological research works in the context of translational research at the German Center for Diabetes Research Changes in the effect on the activity of the underlying genes.

additional Information
* Specifically, the team studied the methylation patterns, that is, the presence or absence of methyl groups on the DNA. Through high-throughput measurements, these methylation patterns can now be studied relatively quickly and on a large scale.

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

*** Some of these could subsequently also be confirmed in adipose tissue, demonstrating 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