In the largest study of its kind to date, Cambridge researchers have looked at why some people manage to stay thin while others gain weight easily. They have found that the genetic dice are loaded in favour of thin people and against those at the obese end of the spectrum.
More than six in ten adults in the UK are overweight, and one in four adults is obese. By age five, almost one in four children is either overweight or obese. Excess weight increases the risk of related health problems including type 2 diabetes and heart disease.
While it is well known that changes in our environment, such as easy access to high calorie foods and sedentary lifestyles, have driven the rise in obesity in recent years, there is considerable individual variation in weight within a population that shares the same environment. Some people seem able to eat what they like and remain thin. This has led some people to characterise overweight people as lazy or lacking willpower.
Professor Sadaf Farooqi’s team were able to recruit 2,000 people who were thin (defined as a body mass index (BMI) of less than 18 kg/m2) but healthy, with no medical conditions or eating disorders. They worked with general practices across the UK, taking saliva samples to enable DNA analysis and asking participants to answer questions about their general health and lifestyles. It is thought to be the only cohort of its kind in the world and the researchers say that the UK’s National Institute for Health Research – the National Health Service’s research infrastructure – strongly enabled and supported their research.
Our DNA comprises of a sequence of molecules known as base pairs, represented by the letters A, C, G and T. Strings of these base pairs form genetic regions (which include or make up our genes). Our genes provide the code for how our body functions and changes in the spelling – for example, a C in place of an A – can have subtle or sometimes dramatic changes on features such as hair colour and eye colour but also on a person’s weight.
The team found several common genetic variants already identified as playing a role in obesity. In addition, they found new genetic regions involved in severe obesity and some involved in healthy thinness.
To see what impact these genes had on an individual’s weight, the researchers added up the contribution of the different genetic variants to calculate a genetic risk score.
Importantly, the team also showed that thin people, had a much lower genetic risk score – they had fewer genetic variants that we know increase a person’s chances of being overweight
Three out of four people (74%) in the STILTS cohort had a family history of being thin and healthy and the team found some genetic changes that were significantly more common in thin people, which they say may allow them to pinpoint new genes and biological mechanisms that help people stay thin.
The research was funded by the European Research Council and Wellcome.