Apr 12, 2007
They found people with two copies of a "fat" version of a gene had a 70% higher risk of obesity than those with none, and weighed 3kg (6.5lb) more.
The work in Science by the Peninsula Medical School and Oxford University studied data from about 40,000 people.
The findings suggest that although improving lifestyle is key to reducing obesity, some people may find it harder to lose weight because of their genes.
Half of white Europeans carry one copy of the variant and one in six has two copies, experts estimate.
The authors say their work, funded by the Wellcome Trust, could improve understanding of obesity and eventually help prevent it, as well as an illness it is linked to.
Obesity is associated with an increased risk of type two diabetes, and the investigators first identified the FTO gene when looking for differences between the genomes of people with type two diabetes and people without diabetes.
People with type two diabetes were more likely to have a particular variant of the FTO gene, which was also shown to be linked to increased body weight.
The variant making people fatter differed from the other version of the FTO gene by a single mutation in the DNA sequence.
The team then looked at other studies involving 40,000 people searching for this FTO mutation, and confirmed that it was associated with body weight.
People carrying one copy of the "fat" FTO variant had a 30% increased risk of being obese compared to a person with no copies of that version.
Those carrying two copies of the variant had a 70% increased risk of being obese, and were on average 3kg (6.6lb) heavier than a similar person with no copies.
Professor Andrew Hattersley of the Peninsula Medical School said this could explain why two people can seem to eat the same things and do the same amount of exercise yet one may struggle to lose weight more than the other.
He said: "The typical message has been that if you are overweight it is due to sloth and gluttony and it is your fault.
"This work is suggesting that there is also a genetic component."
And he said although a 3kg difference in weight sounds relatively small, it is enough to make a big change in the risks of obesity.
Dr Sadaf Farooqi of the Department of Clinical Biochemistry at the University of Cambridge said: "This study is important because it has yielded evidence for the first obesity susceptibility gene.
"Understanding the genetic susceptibility to weight gain will make an important contribution to the prevention and treatment of obesity."
The team does not yet know exactly what the FTO gene does or how the different variants work to influence body weight.
But they hope further research to understand the gene may lead to the unravelling of the basic biology of obesity.
Dr Mark Walport, director of the Wellcome Trust, said this could have very helpful consequences for public health as about one in six white Europeans carried two copies of the variant.
"Obesity is one of the most challenging problems for public health in the UK," he said.
"The discovery of a gene that influences the development of obesity in the general population provides a new tool for understanding how some people appear to gain weight more easily than others."