Common Genetic Link to Obesity Is Discovered
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By NICHOLAS WADE
Published: April 18, 2006
A genetic variation predisposing people to obesity has been detected by a team of researchers at Boston University and elsewhere. Though the gene is expected to be just one of the many that contribute to the disease, its detection raises hopes that the others may be discovered within the next five years or so, said Michael F. Christman, a leader of the team.
Although several obesity-related genes are already known, they affect specific families and are very rare in the general population. The new genetic variant is common, occurring in 10 percent of European and African-American populations. ''We think this will be the first of many common variants that cause obesity,'' said Alan Herbert, another leader. The finding is reported in the current issue of the journal Science.
The team scanned genetic variations in people participating in the Framingham Heart Study, a long-running survey of heart disease. They found a link between obesity and a short section of the genome that lies between two genes. One gene is of unknown function, but the other, known as Insig2, is well known as a regulator of fatty acid and cholesterol synthesis.
So it seems likely, though is not yet proved, that the genetic variant influences the control of the Insig2 gene in a way that can lead to obesity.
Because the variant is found in African populations, it must have arisen before modern humans left Africa some 50,000 years ago. It was harmless until modern times, when some new aspect of the human environment, presumably high-calorie food, interacted with it to raise the risk of obesity.
Those who inherit two copies of the variant, one from each parent, have a 22 percent extra risk of becoming obese, Dr. Herbert said. There may be an extra risk for those who inherit one copy, but it was too small to measure.
The team replicated their finding in several populations but not among participants in the Nurses' Health Study, a source of many health recommendations. For reasons not yet understood, the study had too few obese members to make any statistical link to the variant gene.
Dr. David Altshuler, a medical geneticist at the Broad Institute in Cambridge, Mass., said the team presented ''quite strong evidence'' that it had found the first common genetic variant influencing obesity but that, like all scientific findings, it needed to be confirmed by others.
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