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Genetic variant discovered that protects against obesity

12 July 2021
Appeared in BioNews 1103

A large-scale study has identified genetic variants strongly associated with regulating body weight. 

In one of the most extensive genetic studies of obesity to date, researchers from the USA, UK, Sweden, and Mexico joined forces to identify genetic variations associated with higher and lower lower body mass index (BMI). They found variants in 16 genes that were associated with BMI – many of which were expressed in the brain region responsible for hormone regulation. A gene called GPR75 was found to have the strongest association with body weight, and genetic variants of this gene were correlated with a lower BMI and body weight, and a 54 percent reduced risk of obesity.

'Discovering protective genetic superpowers, such as in GPR75, provides hope in combating global health challenges as complex and prevalent as obesity,' said Dr George Yancopoulos, co-author of the study published in Science, and president and chief scientific officer at Regeneron Genetics Centre (RGC), headquartered in Tarrytown, New York. 

In order to investigate the role of genetics in obesity, the research team led by RGC, carried out exome sequencing of over 600,000 people with a range of body weights, from the USA, UK, and Mexico. They then used this data to identify rare protein-coding gene variants that had a significant impact on the amount of fat tissues individuals stored.

Upon discovery of the GPR75 variations that were correlated with lower risk of obesity, researchers then deleted GPR75 in mice and found that this resulted in resistance to weight gain when put on a high-fat diet. This suggests that inhibition of the GPR75 protein could potentially be used therapeutically to treat obesity.

'While the behavioural and environmental ties to obesity are well understood, the discovery of GPR75 helps us put the puzzle pieces together to better understand the influence of genetics. Further studies and evaluation are needed to determine if reducing weight in this manner can also lower the risk of conditions commonly associated with high BMI, such as heart disease, diabetes, high blood pressure and fatty liver disease,' said Dr Christopher Still, director for the Geisinger Obesity Research Institute at Geisinger Medical Center in Danville, Pennsylvania and an author of the study.

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