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GEN News Highlights : Sep 23, 2013

Explication of Lifestyle-Metabotype Links Deemed Feasible

After conducting an epigenome-wide association study between DNA methylation and metabolic traits, scientists conclude that DNA methylation plays an important role in regulating human metabolism. The scientists, based at the Institute of Genetic Epidemiology (IGE) and the Research Unit Molecular Epidemiology (AME) at Helmholtz Zentrum München, assessed 649 blood metabolic traits from 1,814 participants in a large, long-term regional study that is following the effects of environmental factors, behavior, and genes. Then they searched for associations with the methylation of more than 457,000 loci in DNA. The analysis showed that the methylation of 28 DNA segments changed a number of important metabolic processes.

The study, “Epigenetics meets metabolomics: an epigenome-wide association study with blood serum metabolic traits,” which was published September 20 in Human Molecular Genetics, describes how the Infinium HumanMethylation450 BeadChip platform was used to identify two types of methylome-metabotype associations. The first association is driven by an underlying genetic effect; the second is independent of genetic variation and potentially driven by common lifestyle-dependent factors.

“This study gives us new insights into how lifestyle factors can influence metabolism via the resulting alterations in the DNA,” said Christian Gieger, Ph.D., 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.”

In the relevant DNA regions, there were also already known disease-related genes. For example, the TXNIP gene that regulates glucose metabolism 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, specifically those with corresponding biological functions.

The study’s authors were clear that they had demonstrated the usefulness of epigenome-wide association studies, particularly with large numbers of metabolic traits in big population cohorts, but they were also frank about the limitations of their study: “We did not observe similarly strong effects of DNA methylation on metabotypes compared to what we previously reported for associations of genotype with metabotypes. We also found that results of associations from EWAS with metabolic traits may be difficult to interpret in terms of causality, and that it is hard to distinguish between true functional association and mere correlation that is driven by an unidentified common factor.”

Nonetheless, the authors say that their results shed light on the role of DNA methylation in human metabolism, and indicate that their data may now be used in future studies where a role of DNA methylation in the etiology of complex disorders is suspected.