Genetic Variant Increases Risk of Obesity

The trait is found in 10 percent of people, study says

THURSDAY, April 13, 2006 (HealthDay News) -- Scientists say they've identified a genetic quirk that leads to obesity, and they add that more genetic variants are waiting to be reported.

There's no immediate practical application of the finding, said Michael F. Christman, chairman of genetics and genomics at Boston University Medical School, and a member of the team reporting the discovery in the April 14 issue of Science. But it could someday lead to more effective anti-obesity drugs, he noted.

About half the risk of obesity is determined by the genes people carry, and half of that risk is determined by eight to 10 genes, Christman said. So, the just identified genetic variant, which sits on chromosome 2, is associated with about 5 percent of obesity, he said.

The variant is present in about 10 percent of people around the world, the researchers reported. It is physically close to a gene designated INSIG2, which is involved in fat metabolism. That location suggests it could influence the functioning of the INSIG2 gene, which produces a protein that inhibits production of fatty acid and cholesterol, the researchers said. But more work is needed to say exactly how the relationship between the genes works.

The discovery was made by applying data from the Human Genome Project to people in the long-running Framingham Heart Study and then verifying the relationship in other groups of people around the world, Christman said.

"What we did was to look at 116,000 different points across the human genome where people vary in their sequence," he said. "You know, our genomes are 99.9 percent the same, and it's that one-tenth of 1 percent that makes us different."

Since details on obesity are collected in the Framingham study, the researchers were able to relate this one genetic variant to a propensity for overweight. "Further work showed the same association with obesity in populations all around the world, Europeans, Africans and children," Christman said.

The study has detected other genetic variants associated with obesity in Framingham participants, and they are being checked to see if there is the same association in other groups of people, he said.

"We think the other nine or so genes will be found very soon," Christman said. "Others are doing the same thing. Ours is one of the first, but there will be a flood of these over the next several years."

How will the information gathered in these studies be used? Not in way many people might assume -- genetic testing to determine susceptibility to obesity, Christman said. Rather, it will be used to identify molecular processes in the human body that make people fat, he said.

Once the molecular pathways of obesity are known, researchers could use that knowledge to develop drugs targeting the pathways, Christman said. That could drive down the cost of drug development and result in better drugs, he said.

The discovery was made in a collaboration involving institutions in the United States and Europe. Researchers at the Harvard School of Public Health developed statistical methods used in the analysis, and studies in other populations were done by researchers in Germany and at Loyola University in Chicago, among others.

More information

For more on the role of genetics in obesity, visit the American Obesity Association.

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