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Merck Scientists Apply Innovative Research Method to Identify Changes in Gene Networks Linked to Obesity

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Merck & Co., Inc. has announced the publication of two studies providing evidence that genetic susceptibility to obesity involves changes in entire networks of genes and is not limited to mutations in several specific genes.

The work also showcases how genomic techniques may be used to understand the complex changes at the root of common diseases where multiple complex genetic changes are thought to be involved. The studies were published online in the peer-reviewed journal Nature.

Scientists at Merck Research Laboratories (MRL) and their collaborators performed genetic and gene expression analysis of tissues from a model of metabolic syndrome (a group of conditions that increases the risk of cardiovascular disease and diabetes) and a human population known to be susceptible to obesity.

The resulting data were analyzed using powerful computational methods that integrate data from several sources to identify networks of gene interactions altered in individuals susceptible to obesity.

“These studies strongly support the theory that common diseases such as obesity result from genetic and environmental disturbances in entire networks of genes rather than in a handful of genes,” said Eric E. Schadt, scientific executive director of Genetics at MRL and a senior author on both studies. “If diseases like obesity are the result of complex networks of genes, the accurate reconstruction of these networks will be critical to identifying the best therapeutic targets.”

Much of the emphasis of biomedical research today is directed towards advancing knowledge of the genetic basis of disease and understanding whether DNA variations associated with certain conditions actually contribute to disease or merely act as signposts. The novel approach pioneered by MRL scientists advances the understanding of how multiple; complex DNA variations lead to alterations in entire gene networks that increase an individual's susceptibility to disease.

"The combination of scientific excellence and a focus on patients is the foundation of our work at Merck Research Laboratories," said Kathleen M. Metters, senior vice president, World Wide Basic Research, MRL. "The publication of this important research builds on our history of innovation at Merck and underscores our ongoing commitment to translating breakthrough research into the development of safe and effective medicines."