Gene Deletions May Lead to Severe Obesity

While there is no doubt that our current obesogenic environment is the major driver of the obesity epidemic there is also no doubt that these environmental factors don’t affect everyone to the same degree. Indeed, there is now largely consensus amongst experts that the question of who will get obese and who won’t, given that we are all more or less exposed to the same environmental pressures, is largely determined by our genetic make up (yes, genes also influence behaviour!).

This is even more true for those individuals who make up the rapidly growing group of people with severe obesity – anyone, who believes that you can get to weighing over 350 lbs or more simply by making wrong “choices” probably also still believes in Santa Claus and can’t wait for the Easter Bunny.

Yesterday, the journal Nature reported another study that shows how genetic mutations can markedly increase the risk for severe obesity.

In this large multicentre study headed by my friend and colleague Philippe Froguel, the investigators found a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of a surprisingly large area of chromosome 16 (593 kilobases at 16p11.2) and who also presented with some cognitive deficits.

Subsequently, they identified 19 similar deletions in genome wide association data in 16,053 individuals from eight European cohorts. None of these deletions were found in healthy non-obese controls and were estimated to account for 0.7% of the morbid obesity cases in the dataset.

Interestingly, the parents of some of these index cases also had this deletion and were likewise obese. The cases with the deletion tended to be born with a normal weight but then became overweight at childhood and severely obese as adults.

Unfortunately, this large stretch of chromosome 16 contains many different genes (as many as 30) and it is not clear from these studies exactly which or how these missing genes contribute to the severe obesity phenotype.

Nevertheless, given that this is neither the first genetic defect to be associated with severe obesity nor likely to be the last one of what is believed to be a relatively large number of genetic mutations that have yet to be found, this report should come as a strong warning to anyone who believes that severe obesity is solely a self-inflicted condition resulting purely from poor “choices”.

Copenhagen, Denmark