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Epigenetics
22.12.2016

Overweight Affects DNA Methylation

The extra pounds you gain during the holidays will not only show up on your hips but will also affect your DNA. This is the result of a large-scale international study coordinated by Helmholtz Zentrum München, a partner in the German Center for Diabetes Research, which has now been published in ‘Nature’. The study shows that a high BMI leads to epigenetic changes at nearly 200 loci of the genome – with effects on gene expression.

Epigenetics

Overweight affects DNA methylation. Source: Fotolia/SSilver

While our genes do not change in the course of life, our lifestyle can directly influence their surroundings. Scientists speak here of the epigenome (Greek epi: over, outside of, around), which refers to everything that happens on or around the genes. Up to now there has not been much research on how the epigenome is altered as a result of being overweight. “This issue is particularly relevant because an estimated one and a half billion people throughout the world are overweight,” said first author Dr. Simone Wahl of the Research Unit Molecular Epidemiology (AME) at Helmholtz Zentrum München, “especially considering that being overweight can have adverse consequences and lead to diabetes and diseases of the cardiovascular and metabolic systems.”

World’s largest study on BMI and epigenetics

For this reason, the international research team led by Dr. Christian Gieger and Dr. Harald Grallert of the AME (as well as Jaspal Kooner and John Chambers of Imperial College London) examined possible correlations between body mass index (BMI) and epigenetic changes.* Using state-of-the-art technology, the team carried out the world's largest study so far on the subject.

The scientists examined the blood samples of over 10,000 women and men from Europe. A large proportion of these were inhabitants of London of Indian ancestry, 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 dependent on the BMI. They then tested these candidate loci in blood samples of an additional 4,874 subjects and were able to confirm 187 of these***. Further studies and long-term observations also indicated that the changes were predominantly a consequence of being overweight – not the cause.

Significant changes also in the expression of inflammatory genes

“In particular, significant changes were found in the expression of genes responsible for lipid metabolism and substrate transport, but inflammation-related gene loci were also affected,” said group leader Harald Grallert. From the data, the team was also able to identify epigenetic markers that could predict the risk of type 2 diabetes.  

“Our results allow new insights into which signaling pathways are influenced by obesity“, said Christian Gieger, head of the AME. "We hope that this will lead to new strategies for predicting and possibly preventing type 2 diabetes and other consequences of being overweight.” Next, within the framework of translational research in the German Center for Diabetes Research, the researchers want to investigate in detail how the epigenetic changes affect the expression of the underlying genes.

Further Information

* Specifically, the team investigated the methylation patterns, i.e. the presence or absence of methyl groups on the DNA. By means of high-throughput measurements, these methylation patterns can now be investigated 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 population from Italy

*** Some of these have also been confirmed in adipose tissue, indicating that changes in gene regulation in disease-relevant tissues are also visible in the blood.

Background:
Helmholtz Zentrum München has extensive expertise in the field of genetic and epigenetic causal research on metabolic diseases: As recently as July 2016, the researchers were involved in the world’s largest genetic study on type 2 diabetes, which was likewise published in the renowned journal Nature. Link to press release. Furthermore, already in March 2016 scientists of Helmholtz München showed that diet-induced obesity and diabetes can be passed on epigenetically to the offspring via both oocytes and sperm. Link to related press release.

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

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Research Unit of Molecular Epidemiology (AME) analyses population-based cohorts and case studies for specific diseases, using genomics, epigenomics, transcriptomics, proteomics, metabolomics and functional analyses. The aim of this research unit is to decipher the molecular mechanisms of complex diseases like type 2 diabetes or obesity. The unit administers the biological specimen repository of the Department of Epidemiology and stores the samples for national and international projects. 

The Institute of Epidemiology II (EPI II) focuses on the assessment of environmental and lifestyle risk factors which jointly affect major chronic diseases such as diabetes, heart disease and mental health. Research builds on the unique resources of the KORA cohort, the KORA myocardial infarction registry, and the KORA aerosol measurement station. Aging-related phenotypes have been added to the KORA research portfolio within the frame of the Research Consortium KORA-Age. The institute’s contributions are specifically relevant for the population as modifiable personal risk factors are being researched that could be influenced by the individual or by improving legislation for the protection of public health. 

Research at the Institute of Genetic Epidemiology (IGE) focuses on planning, realization and analysis of projects regarding the identification of genetic factors responsible for complex traits. This involves application, further development and implementation of a variety of statistical methods to address specific aspects such as rare genetic variants, mitochondrial DNA, gene-gene and gene-environment interactions, family studies, and the handling of population structures. The elucidation of disease-relevant genetic factors as well as their inclusion into models of disease risk provides the basis of individualized approaches to treatment or prevention.

The Institute of Human Genetics (IHG) at the Helmholtz Zentrum München and the Technical University of Munich: The Institute is concerned with identifying genes associated with disease and characterizing their functions. The main aim of the research projects is to develop disease-related genetic variation in humans and mice as well as to develop chromosome analysis techniques and new methods for dealing with specific issues in the sphere of pre- and post-natal diagnostics and tumor cytogenetics. 

The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich.