Most recent update: Tuesday, December 12, 2017 - 16:38

Bariatric News - Cookies & privacy policy

You are here

Genetics

UK10K: genetic variants linked to childhood obesity

Genome-wide SNP association study in severe early-onset obesity
Discovery could lead to new drugs in battle against obesity

Researchers have identified four genes newly associated with childhood obesity, which could lead to promising new drugs against childhood obesity.

The research, published in the journal Nature Genetics, also found an increased burden of rare structural variations in severely obese children, which can delete sections of DNA that help to maintain protein receptors known to be involved in the regulation of weight. These receptors are key targets for the development of new drugs against 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-lead author of the study 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."

The identification of four new genetic variants linked with severe childhood obesity brings the list of DNA variants associated with obesity to just over 50.

The team found that different genes can be involved in severe childhood obesity, compared with obesity in adults. Rare genetic changes in one of the newly associated genes, LEPR, are known to cause a severe form of early onset obesity. The team identified a more common variant in this gene, found in 6% of the population, that can increase a person’s risk of obesity. This finding is an example of where rare and more common variations around the same gene or region can influence the risk of severe obesity.

Some of the children in this study had an increased number of structural variations of their DNA that delete G-protein coupled receptors, important receptors in the regulation of weight. These receptors are key targets for current drug development and may have potential therapeutic implications for obesity.

The researchers, who are part of the UK10K project, are now exploring all the genes of 1,000 children with severe obesity in whom a diagnostic mutation has not been found. This work will find new severe mutations that may explain 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-lead 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 discovery is part of a wider search for the genes involved in increasing a person’s risk of becoming overweight when exposed to an “obesogenic environment” of high-calorie food and inactivity – which is known to affect some people more than others.

Some of the genetic variations revealed by the study were rare but others are relatively common, suggesting an interaction between genetics and environment, which could explain why certain children become obese while others do not even when they share a similar upbringing.

Obesity among British children aged between two and ten has risen since 1995 from 10.1 per cent to 13.9 per cent in 2011. This rise cannot be due to a change in genes alone, because it takes many generations to alter the frequency of genetic mutations in the population.

However, it is clear that some children are predisposed to become obese when exposed to a high-calorie diet and lack of exercise. It is this genetic predisposition that scientists are trying to understand.

“There have always been some kids who are very heavy but this has in the past been a small number,” said Farooqi. “Now, because of the environment they are growing up in, we are seeing many more children in this category.”

Some of the genetic variations linked with obesity are associated with genes involved in regulating leptin, a hormone known to act as an appetite suppressor. Variations of a gene known as FTO are thought to increase the chances of obesity because of the gene’s effect on leptin levels in the body.

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

Want more stories like this? Subscribe to Bariatric News!

Bariatric News
Keep up to date! Get the latest news in your inbox. NOTE: Bariatric News WILL NOT pass on your details to 3rd parties. However, you may receive ‘marketing emails’ sent by us on behalf of 3rd parties.