A ‘thrifty’ variant contributes to obesity in Samoans

A genetic variant in the gene CREBRF that increases the risk of obesity in Samoans is reported in a study published online this week in Nature Genetics. The variant is predicted to be thrifty - increasing fat storage while decreasing energy use - which may have been beneficial to Samoans in the past during times of food scarcity.

Samoans have among the highest prevalence of obesity in the world. In 2010, 80% of Samoan men and 91% of Samoan women were overweight or obese, likely owing to changes in modern diets and reduced physical activity. Samoa is also unique because it has remained relatively isolated throughout its 3,000-year history. This has led to a lower level of genetic variability among Samoans than in most mainland populations, a phenomenon known as a founder effect.

Stephen McGarvey and colleagues conducted a genome-wide association study in 3,072 Samoans to identify genetic variants associated with traits related to obesity. The researchers find a variant in the gene CREBRF associated with increased body mass index (BMI), percentage body fat and fasting glucose levels, among other obesity-related traits. The variant’s effect on BMI is the largest of any known common risk variant. As a consequence of the founder effect, the variant is common in Samoans (approximately 45% of Samoans have 1 or 2 copies) but is extremely rare in other populations. Future work is needed to better understand the function of the CREBRF variant and whether this discovery can help improve understanding of obesity in non-Samoan populations.

doi: 10.1038/ng.3620

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