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Four new genes and increased rare structural variations in genetic material have been linked to severe childhood obesity.

Researchers found that structural variations in obese children can delete sections of DNA which help to maintain protein receptors involved in weight regulation. By targeting these receptors, scientists may be able to develop new drugs to fight obesity.

Children with severe obesity are likely to have a genetic predisposition, this study helped to clarify contributing factors from common and rare variants around specific genes and genetic regions.

"We've known for a long time that changes to our genes can increase our risk of obesity. For example, the gene FTO has been unequivocally associated with BMI, obesity and other obesity-related traits," said Dr. Eleanor Wheeler, first author from the Wellcome Trust Sanger Institute.

 "In our study of severely obese children, we found that variations in or near two of the newly associated genes seem to have a comparable or greater effect on obesity than the FTO gene: PRKCH and RMST."

Compared to obesity in adults, researchers found different genes to be involved in severe childhood obesity. One of the newly associated genes is LEPR. A more common variant in this gene was found in six percent of the population and is associated with a severe form of early onset obesity.

The study found some children to have an increased number of structural variations in their DNA which deleted G-protein coupled receptors. According to researchers, these receptors are may have a potential therapeutic implication for obesity.

"Some children will be obese because they have severe mutations, but our research indicates that some may have a combination of severe mutations and milder acting variants that in combination contribute to their obesity," said Professor Sadaf Farooqi, co-author from the University of Cambridge. "As we uncover more and more variants and genetic links, we will gain a better basic understanding of obesity, which in turn will open doors to areas of clinically relevant research."

Researchers are now studying the genes of 1000 children with severe obesity which have not displayed a diagnostic mutation. This is part of the UK10K project which hopes to find new severe mutations explaining the causes of obesity in other children.

"Our study adds evidence that a range of both rare and common genetic variants are responsible for severe childhood obesity," said Dr. Inȇs Barroso, co-author from the Wellcome Trust Sanger Institute. "This work brings us a step closer to understanding the biology underlying this severe form of childhood obesity and providing a potential diagnosis to the children and their parents."

The study was funded by the Wellcome Trust at the MRC and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and published online in Nature's Genetics.