People with most ‘fat genes’ have 25 times higher risk of severe obesity, study says

‘DNA is not destiny but those with a high genetic predisposition have to work much harder to maintain a normal weight’

Genetics may account for as much as 10 per cent of a person’s obesity risk (Getty)

People with the most “fat genes” are around 25 times more likely to become severely obese in their lifetime than people whose DNA has the greatest protective effect, a study has found.

While diet, exercise, ill health and hundreds of other factors are the major determiners of obesity, US researchers have found that genetics can have a “profound effect”.

The authors said 10 per cent of a person’s obesity risk may be determined by their DNA. In the participants in the study this amounted to an average difference of two stone (13kg) by middle age, between the most affected and protected groups.

The researchers, led by MIT and Harvard Medical School, have developed this into a genetic “risk score” which can show how great someone’s risk might be, and which could potentially be used from birth to take protective action.

“We have always had a hunch that some people may have been born with a genetic profile that predisposes them to obesity, and we now confirm that this is both true and quantifiable,” said Dr Amit Khera, one of the authors and a cardiologist at Massachusetts General Hospital.

However, Dr Khera said, “DNA is not destiny” when it comes to weight gain and a “healthy diet and exercise can offset a genetic predisposition”.

“It is also likely true that those with a high genetic predisposition have to work much harder to maintain a normal weight,” he added.

The research, published in the journal Cell, analysed more than 2 million genetic variants known to have an impact on body-mass index (BMI), some which will increase obesity and some which will be protective.

This data comes from more than 300,000 people who have added their health and genetic information to research libraries, however, the mostly European population means the applicability of findings to other groups is less certain.

It found that the top 10 per cent of people with the most genetic variants linked to a higher BMI also had double the risk of weight-related type 2 diabetes of those in the most protected category.

Because these are average scores there could be much heavier or lighter individuals within both the most genetically at risk group, and the least.

But looking at them as a group the researchers said that by age three they could begin to see the effects of the higher genetic risk showing in children’s weight. By age eight this high risk group were 3.5kg heavier.

While these findings don’t affect the weight they are born, the effects begin to be seen by childhood and play out into adulthood, also affecting the risk of weight-related conditions like type 2 diabetes.

“The score is associated with only minimal differences in birth weight, but it predicts clear differences in weight during early childhood and profound differences on weight trajectory and risk of developing severe obesity in subsequent years,” says senior author Sekar Kathiresan of the Broad Institute.

The authors say that these genetic risk scores could be used in future to minimise their genetic risks by making healthier life choices. However, their usefulness at predicting risks when so many other factors are involved remains controversial.

“While outstanding questions include whether genetic predisposition to severe obesity can be reduced, these findings should put further pressure on health departments and ministries to recognise obesity as a disease,” said Dr Rishi Caleyachetty, of Warwick Medical School, who was not involved in the study.

Professor Tim Frayling of the University of Exeter said spotting people with the most “fat genes” could be particularly helpful in childhood when diet and lifestyle interventions can have the most benefit.