This world-first epigenome-wide association study (EWAS) of modified genes and metabolites has been now published in the journal Human Molecular Genetics.
In the course of life, aging processes, environmental influences and lifestyle factors such as smoking or diet induce biochemical alterations to the DNA. Frequently, these lead to DNA methylation, a process in which methyl groups are added to particular DNA segments, without changing the DNA sequence. Such processes can influence gene function and are known as epigenetics. Scientists of the Institute of Genetic Epidemiology (IGE) and the Research Unit Molecular Epidemiology (AME) at Helmholtz Zentrum München are seeking to determine what association exists between these epigenetic processes and the health consequences, in particular for the metabolism.
To this end, the team led by Christian Gieger (IGE) and Melanie Waldenberger (AME), in in collaboration with Karsten Suhre of Weill Cornell Medical College in Qatar analyzed blood samples from more than 1800 participants of the KORA study *. In doing so, they analyzed more than 457,000 loci in the DNA as to biochemical alterations and compared them with the concentrations of 649 different metabolites. The analysis showed that the methylation of 28 DNA segments changed a number of important metabolic processes.
In the relevant DNA regions there were also already known disease-related genes: for example, the TXNIP gene that regulates glucose metabolism and is associated with the development of diabetes mellitus. Appropriately, with the methylated TXNIP there were altered concentrations of metabolites from the lipid and glucose metabolism. Also genes that are known to be biochemically altered due to smoking affect different metabolic activities, and specifically those with corresponding biological functions.
“This study gives us new insights into how lifestyle factors can influence metabolism via the resulting alterations in the DNA,” said Gieger, research group leader at the IGE. “We can now use these results to develop new diagnostic and therapeutic approaches for lifestyle-related diseases such as diabetes.”
*KORA(Kooperative Gesundheitsforschung in der Region Augsburg)
For more than 20 years, the research platform Cooperative Health Research in the Augsburg Region (KORA) has been collecting and analyzing data on the health of thousands of people living in the Augsburg region. The objective is to elucidate the effects of environmental factors, behavior and genes. KORA focuses on the development and course of chronic diseases, in particular myocardial infarction and diabetes mellitus. Risk factors are analyzed with regard to individual health behavior (e.g. smoking, diet, exercise), environmental factors (e.g. air pollution, noise) and genetics. From the perspective of health care research, questions regarding the utilization of health care resources and the cost of health care are also studied. www.helmholtz-muenchen.de/kora
Petersen, A.-K. et al. (2013). Epigenetics meets metabolomics: An epigenome-wide association study with blood serum metabolic traits, Human Molecular Genetics, doi: 10.1093/hmg/ddt430
As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,100 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 34,000 staff members. www.helmholtz-muenchen.de
Research at the Institute of Genetic Epidemiology (IGE) is concerned with genetic statistics. This encompasses the planning, execution and analysis of gene mapping projects related to complex diseases as well as the development and implementation of new statistical methods. The activities extend to genome-wide association studies and linkage analyses (family studies) of a wide variety of diseases. A focus is on phenotypes that are studied within the framework of the population-based KORA cohort. The aim of the Institute is to contribute to the elucidation of the genetic causes of complex diseases.
TheResearch 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.
Dr. Christian Gieger, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Institute of Genetic Epidemiology, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49-89-3187-4106 – E-Mail