A new study published today in Nature suggests that approximately seven in every thousand morbidly obese people are missing a section of their DNA containing approximately 30 genes, which may be having a dramatic effect on their weight.

Researchers 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 over 30, which means they were obese.

A study the genomes of 16,053 people who were either obese or normal weight, (with a BMI between 18.5 and 25), from eight European cohorts revealed 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.

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.

Previous research had 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. Today's research 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.

People inherit two copies of their DNA, one from their mother and one from their father. Sometimes, missing one copy of one or several genes - as in the individuals identified in this latest study - can have a drastic effect on the body.

The researchers believe there may be other genetic deletions, in addition to those identified today, 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.

Professor Philippe Froguel, lead author of the study from the School of Public Health at Imperial College London, said: "Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic. It is becoming increasingly clear that for some morbidly obese people, their weight gain has an underlying genetic cause. 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."






Citation: Walters et al.,  'A new highly penetrant form of obesity due to deletions on chromosome 16p11.2. Nature, 2010', February 2010,  463 (7281): 671; doi: 10.1038/nature08727