Missing DNA may be responsible for causing some people to be morbidly obese, according to research published in the journal Nature. Researchers from Imperial College London and ten other European Centers say that the deletion of DNA containing approximately 30 genes was found in around seven in every 1,000 morbidly obese people. The researchers say the deletion was not present in normal weight people.

 

Researchers believe that the weight problems of around one in twenty morbidly obese people are due to known genetic variations, including mutations and missing DNA. Many more obesity-causing mutations, such as the one identified in the study, remain to be found, the researchers say.

 

Previous research identified several genetic variations that contribute to obesity, most of which are single mutations in a person's DNA that change the function of a gene. The researchers say their work is the first to clearly demonstrate that obesity in otherwise physically healthy individuals can be caused by a rare genetic variation in which a section of a person's DNA is missing. The researchers do not yet know the function of the missing genes, but previous research has suggested that some of them may be associated with delayed development, autism and schizophrenia.

 

The researchers believe there may be other genetic deletions that increase a person's risk of becoming obese. They hope that by identifying genetic variations causing people to be extremely obese, they can develop genetic tests to help determine the best course of treatment for these individuals.

 

Philippe Froguel, lead author of the study from the School of Public Health at Imperial College London says while the rise in obesity in the developed world is due to an environment with an abundance of unhealthy food and many people getting inadequate exercise, the different way people respond to this environment is often rooted in genetics.

“It is becoming increasingly clear that for some morbidly obese people, their weight gain has an underlying genetic cause,” he says. “If we can identify these individuals through genetic testing, we can then offer them appropriate support and medical interventions, such as the option of weight loss surgery, to improve their long-term health."

 

The Imperial team first identified the missing genes in teenagers and adults who had learning difficulties or delayed development. They found 31 people who had nearly identical deletions in one copy of their DNA. All of the adults with this genetic change had a BMI of more than 30, which means they were obese.

 

The researchers then went on to study the genomes of more than 16,000 people who were either obese or normal weight, (with a BMI between 18.5 and 25), from eight European cohorts. They identified 19 more people with the same genetic deletion, all of whom were severely obese, but did not find the deletion in any healthy normal weight people. This means the genetic deletion was found in seven in every 1,000 morbidly obese people, making it the second most frequent known genetic cause of obesity.

 

People with the deletion tended to be normal weight toddlers, becoming overweight during childhood and then severely obese as adults. The researchers also looked at the genomes of their parents, and found that 11 people inherited the deletion from their mother and four from their father, with ten of the deletions occurring by chance. All the parents with the deletion were also obese.

 

The next step in this research will be to determine the function of the missing genes. Previous studies have suggested that some of the genes may be associated with delayed development, autism and schizophrenia, so the researchers also plan to investigate the possible links between these conditions and obesity.

 

“The method used in the study could also help find novel genetic variations that affect the risk of other conditions,” says Imperial College London’s Froguel. “We identified this variant by first studying very obese individuals, and then homing in on the region of interest in larger, less severely affected groups. This powerful approach could be used to identify genetic influences on other diseases that are poorly understood at present, such as type 2 diabetes.”