Most powerful obesity gene yet boosts risk by 40 per cent

It could be in your DNA. A gene variant that increases a person’s obesity risk by 30 to 40 per cent is the strongest genetic predictor of body weight discovered in humans so far.

Having just one copy of a particular variant of a gene called CREBRF is associated with a 1.5 increase in BMI. For a person weighing 83 kilograms who is 1.75 metres tall, this is the equivalent of putting on 4.6 further kilograms.

The genetic variant was uncovered during a genomic analysis of more than 5000 people in Samoa, where obesity rates are among the highest in the world. Ryan Minster at the University of Pittsburgh, Pennsylvania, and his team found that a quarter of Samoans carry this variant, which may have evolved during their history of colonising the South Pacific. “They had to endure voyages between islands and subsequently survive on those islands,” says Minster.

The CREBRF variant appears to be rare in other populations, but studying how the gene works may help researchers better understand obesity.

Several obesity genes have been documented in the past, but they each have only a small effect on weight. The most well known of these – a variant of a gene called FTO – is associated with a modest 0.4 increase in BMI for every copy carried.

To investigate how CREBRF promotes weight gain, the team genetically engineered fat cells in the lab to express the obesity-associated variant. They found that this caused the cells to store more fat and release less energy, as if they are trying to conserve as much fuel as possible.

This thriftiness is likely to be advantageous during periods of food scarcity, but lead to obesity in times of nutritional excess, says team member Stephen McGarvey at Brown University.

Diets in Samoa have changed, and physical activity has declined. Their genetic thriftiness might explain why 80 per cent of men and 91 per cent of women there are now overweight.

However, the team found no association between the gene variant and diabetes, even though the two conditions normally go hand in hand. In fact, carriers of the CREBRF variant had significantly lower rates of diabetes.

“People with the gene are heavier, but perhaps their risk of disease is not increased,” says Lennert Veerman at the University of Queensland, Australia.

Nevertheless, he says knowing your genetics should not change how you approach your health. “Everybody needs to strive for a healthy lifestyle – people with this gene aren’t special in this respect,” says Veerman.

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