Researchers at Imperial College London [Images], the French National Research Institute CNRS and other international institutions have discovered three new genetic variations that increase the risk of obesity, giving new insight into the reasons why some people become fat and others don't.

They suggest that if each acted independently, these variants could be responsible for up to 50 percent of cases of severe obesity.

According to researchers, the new findings should ultimately provide the tools to predict which young children are at risk of becoming obese.

For the study, the researchers looked at the genetic makeup of obese children under six and morbidly obese adults, most of whom had been obese since childhood or adolescence, and compared this with age matched people of normal weight.

The researchers discovered three previously unidentified genetic variations that increase the risk of severe obesity significantly.

The gene variant most strongly linked to childhood obesity and adult morbid obesity in the study is located near the PTER gene, the function of which is not known.

This variant is estimated to account for up to a third of all childhood obesity, and a fifth of all cases of adult obesity.

The second variant linked to child and adult obesity is found in the NPC1 gene.

Previous studies in mice have suggested that this gene has a role in controlling appetite, as mice with a non-functioning NPC1 gene suffer late-onset weight loss and have poor food intake.

This gene variant accounts for around 10 percent of all childhood obesity and about 14 percent of adult morbid obesity cases.

The final variant is found near the MAF gene, which controls the production of the hormones insulin and glucagon, as well as chains of amino acids called glucagon-like peptides.

These hormones and peptides are known to play key roles in people's metabolisms by metabolising glucose and carbohydrates in the body. Also, glucagon and glucagon-like peptides appear to have a strong effect on people's ability to feel 'full' or satiated after eating.

This variant accounts for about 6 percent of early-onset obesity in children, and 16 percent of adult morbid obesity.

The researchers reached their conclusions by conducting a genome-wide association study of 1,380 Europeans with early-onset childhood obesity and adult morbid obesity, and 1,416 age-matched normal weight controls.

The study revealed 38 genetic markers with a strong association to a higher than normal body mass index, which the researchers evaluated in 14,186 Europeans, identifying three mutations that are significantly linked to obesity.

The study is published in the journal Nature Genetics.

Illustration: Uttam Ghosh