Genetic Links To Obesity
April 8, 2013

Two Research Teams Discover New Genetic Links To Obesity

redOrbit Staff & Wire Reports - Your Universe Online

Two new studies appearing in this week´s edition of the journal Nature Genetics have identified new genetic links to obesity which could lead to new ways to help treat or prevent the condition.

In one study, an international team of researchers identified seven new gene loci (genome regions) linked to obesity, while also demonstrating that the genetic mechanisms that cause extreme body fat are similar in nature to those that cause milder forms of excess weight or obesity.

The study, which was coordinated by Erik Ingelsson, a professor at the Uppsala University Department of Medical Sciences and Science for Life Laboratory, looked at over 260,000 people in an attempt to both identify new genes that increase the risk of obesity and compare genetic factors responsible for extreme obesity with those linked to the rest of the body-mass index (BMI) range.

“We know from experience that genetic factors are important for the emergence of both milder and more extreme forms of obesity, but how much overlap there is between genes that are involved in extreme obesity and normal or slightly elevated BMI has not been examined systematically previously,” Ingelsson said in a statement.

He and his colleagues examined the relationships between 2.8 million gene variants (DNA which differs from one person to another) and various body measurements in 168,267 individuals. They then conducted a follow-up of the 273 variants with another 109,703 people, and through extensive gene mapping, they were able to identify four new genome regions linked to height and seven more associated with being overweight and obese.

“This knowledge is important because it increases the biological understanding of the origins of extreme obesity as well as milder forms of obesity,” Ingelsson said. “Our results suggest that extremely obese individuals have a greater number of gene variants that increase the risk of obesity, rather than completely different genes being involved.”

“In the long term, our findings may lead to new ways of preventing and treating obesity, which is one of the greatest global public health problems of our age,” he added. Their research demonstrates that conclusions gathered from genetic studies of the most extreme cases of a physical characteristic such as obesity could be applied to the rest of the population. That discovery, the researchers say, could help future studies.

The authors of the second study discovered four genes newly associated with severe cases of childhood obesity, as well as a structural variation that can delete sections of DNA that help maintain weight-regulating proteins. Those receptors, the researchers report, could become the focus of future anti-obesity drug development.

“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,” first author Dr. Eleanor Wheeler of the Wellcome Trust Sanger Institute said in a statement. “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.”

Wheeler and her colleagues discovered that the genes involved in severe childhood obesity can be different that those responsible for the condition in adults. Rare genetic changes in one of the new genes (LEPR) have been linked to a severe form of early onset obesity, but the researchers discovered a more common variant of that gene that can also increase a person´s risk of becoming severely overweight.

In addition, some of the children that participated in the study showed an increased number of structural variations in DNA that deletes protein receptors essential to weight regulation. Those receptors, which are known as G-protein coupled receptors, are currently targets for drug development and could also have potential therapeutic implications for obesity, the researchers explained.

“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,” explained University of Cambridge professor and co-lead author Sadaf Farooqi. “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.”

“Our study adds evidence that a range of both rare and common genetic variants are responsible for severe childhood obesity,” added co-lead author Dr. Inȇs Barroso of 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.”