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New 'obesity gene' found in half of Samoan population

1 August 2016
Appeared in BioNews 862

A newly discovered genetic variant in the Samoan population increases obesity risk by 35 percent – the largest effect of any obesity gene.

The study, published in Nature Genetics, analysed the genomes of more than 5000 people in Samoa and found that nearly half had a mutation in a gene called CREBRF. The mutation was linked not just to obesity risk but also to body-fat percentage, abdominal and hip circumference, and other body mass index (BMI)-related measures.

Despite the link with obesity, the team found that 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,' Dr Lennert Veerman from the University of Queensland, Australia, told New Scientist.

Several obesity genes have previously been discovered, but none has such a large effect – having just one copy of the CREBRF variant was associated with an increase in BMI of 1.5 points. For a 1.75-metre tall person weighing 83 kilograms, this is the equivalent of putting on a further 4.6 kilograms. The increased risk of falling into the obese category was 35 percent for those who had a single copy of the gene variant, compared with not having one.

Among Samoans, 38 percent had a single copy of the gene variant and seven percent had two copies. The mutation was virtually non-existent in European populations and present at only very low frequency among East Asians.

To see how the gene worked, the researchers genetically engineered fat cells to express the variant. They found that cells with the gene variant had increased fat storage and decreased energy use. This is an example of a 'thrifty' variant – an idea proposed by epidemiologist James Neel in 1962. This 'thriftiness', or efficiency in using energy, is likely to be advantageous during food scarcity but can lead to obesity in times of nutritional excess.

'Samoans weren't obese 200 years ago,' explained Dr Stephen McGarvey of Brown University, one of the authors of the study. 'The gene hasn't changed that rapidly – it's the nutritional environment that changed that rapidly. Once modern conveniences like motor vehicles and high-calorie foods became prevalent among Samoans, they, like many people around the world, became more prone to obesity.'

Samoa currently has one of the highest obesity rates in the world. In 2003, 68 percent of men and 84 percent of women in Samoa were overweight or obese. In 2010, that had increased to 80 percent of men and 91 percent of women. However, Dr McGarvey strongly cautioned against describing the Samoan obesity problem as genetic inevitability. Despite the CREBRF variant increasing obesity risk more than any other known obesity variant, overall it explains only about two percent of the variation in BMI among Samoans. Other factors such as diet, physical activity, early-life nutrition and growth are also important.

'Don't take this as – you are Samoan, you are fated to be obese,' Dr McGarvey said. 'We don't think that's true. A healthy diet and physical activity are still key to maintaining a healthy weight.'

SOURCES & REFERENCES
A thrifty variant in CREBRF strongly influences body mass index in Samoans
Nature Genetics |  25 July 2016
BMI-Associated Mutation With Potential Energy Conservation Role ID'd In Samoans
GenomeWeb |  25 July 2016
Most powerful obesity gene yet boosts risk by 40 per cent
New Scientist |  25 July 2016
Newly found, 'thrifty' genetic variant influences Samoan obesity
Science Daily (press release) |  25 July 2016
Samoan obesity's gene link
New Zealand Herald |  26 July 2016
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