Merck & Co. published two studies in the journal Nature that provide evidence that genetic susceptibility to obesity involves changes in entire networks of genes and is not limited to mutations in specific genes.
In two related studies, Merck and collaborators report finding a core group of genes that have a causal relationship to disease traits including three previously unknown genes. They used large-scale analyses of data on DNA variations, gene-expression patterns in disease-relevant tissues, and clinical data to identify molecular networks underlying metabolic disorders.
In the first study, Merck researchers and colleagues from the University of California at Los Angeles used liver and fat tissue samples from mice to identify genetic variations associated with obesity, diabetes, and atherosclerosis. The authors then constructed gene networks and identified core groups of genes in these networks that were causally related to relevant traits associated with obesity, diabetes, and heart disease. Based on various analyses, the authors identified and experimentally validated three novel genes causally related to obesity-associated traits: Lpl, Pmp1l, and Lactb.
The second study, which was based on methods developed in the mouse study, involved researchers from Merck, deCODE Genetics, and the National University Hospital in Iceland. The team constructed gene-expression networks associated with obesity traits using blood and fat tissue samples and clinical data from more than 1,000 people in Iceland. A gene-expression network constructed from human fat tissue contained a similar core group of genes found to be causally related to obesity in the mouse study.
Both studies were published in the March 16 issue of Nature.