Study Unveils Networks of Genes Behind Obesity

A novel way to discover networks of genes linked with obesity in mice as well as humans has been discovered, say scientists.

The new approach, which is said to be more comprehensive than the traditional methods used for identifying genes linked with the condition, is currently being used to detect potential drug targets, they say.

Eric Schadt of Seattle-based Rosetta Inpharmatics, who led one of the research teams involved in the project, said that the traditional approach is based on switching on or off genes to see whether it would raise or lower the risk of the disease.

However, the new approach looks at changes in the expression of already-known genes, and finds networks of genes associated with the disease, rather than single switches.

“Instead of the simple ‘turn the light on or off’ analogy, we would view this as a network of these switches,” Nature magazine quoted Schadt as saying.

The researchers collected blood and fat samples from hundreds of Icelanders with the help of experts at an Iceland-based genetics company called deCODE, who analysed the expression of 23,720 known genes in each sample, and correlated the results with the body mass index of each participant.

Their efforts led to the identification of 2,000 genes whose expression is altered in blood cells in obese people.

The researchers said that there were over 17,000 such genes in fat tissue. They were able to group genes into networks that regulated together after finding patterns in the gene expression data.

The Seattle team later looked for the genome for additional DNA sequence variations associated with some of these changes in gene expression.

Although the new approach seems to be similar to a traditional genetic association study, starting with information about altered gene expression gives the researchers a hint about how the variants could be acting to affect obesity.

According to the researchers, their approach yielded thousands of DNA variants, most of which were located near the gene whose expression was altered.

The researchers said that their project confirmed that being heavy can be hereditary, for 70 per cent of the gene expression changes found in fat cells were heritable.

The study also confirmed the importance of the immune system in metabolic disorders like obesity, as a similar study in mice led by Schadt determined that a group of genes related to obesity are also involved in inflammation.

The researchers believe that going beyond a single gene association to studying networks of genes may be useful in identifying new drug targets for other conditions or diseases.

“Through the idea of a network, you increase your chances of finding genes responsible for the phenotypes you are interested in,” says Chiara Sabatti, a biostatistician at the University of California, Los Angeles.

Schadt revealed that the gene-hunting technique was already being used by Merck, and several other labs are gearing up to use it as well.

“We’re not just looking at one gene, that may or may not be druggable. We’re looking at what are the best nodes, or information control points. What’s the best light switch to affect the network maximally?” he said.

Source-ANI
SRM/K