Mark Henderson, Science Editor
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A genetic variation that raises the risk of obesity has been discovered by a British-led research team, offering insight into why some people put on weight while others with similar lifestyles stay slim.
People who inherit two copies of the variant, which lies close to a gene called MC4R, weigh an average of 1.5kg (3.3lb) more than those with none, according to the international study of 90,000 people published in Nature Genetics. The newly identified effect also combines with a gene known to influence obesity, called FTO. People who have the most damaging versions of both genes tend to be between 3.5kg and 4.5kg heavier than those with the “slimmest” possible genetic profile.
One quarter of British adults are classified as obese, and half of men and a third of women are overweight.
Though it has long been known from family studies that obesity is influenced by genetics, scientists struggled to find common DNA variations responsible for such effects. Two are now known, thanks to advances in gene-hunting technology, and these could potentially inform the design of drugs that help weight control.
Inês Barroso, of the Wellcome Trust Sanger Institute, a research leader, said: “The precise role in obesity of genetic variants in FTO and near MC4R remains to be discovered, but we can begin to understand the biological consequences of these variants.”
The discovery also illuminates the importance of “junk DNA” — the 98 per cent of the genome that does not contain protein-making genes, and was once thought to have no function. This junk, however, is increasingly recognised to have a critical role, as it contains genetic switches that turn gene activity up or down to influence protein manufacture.
The new variant linked to obesity may be such a genetic switch: it lies in a region of junk DNA, but very close to a gene called MC4R. Rare mutations in this gene cause early-onset obesity in a few children. The variant, which is much more common, is thought to turn down expression of the normal MC4R gene.
About 5 to 7 per cent of people of Caucasian background have two copies of the new variant, and 35 to 38 per cent have one. A second study led by Jaspal Kooner, of Imperial College London, has found that the variant is significantly more common among people of Indian ancestry.
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