Many of 97 ‘weight gene’ variants identified work by changing brain’s regulation of appetite, according to research published in Nature

More than a fifth of the weight differences between people can be explained by common “obesity genes”, according to research that confirms some people are naturally at greater risk of becoming overweight.

The study, involving more than 300,000 people, highlights 97 gene variants that have a particularly powerful influence on weight, many of which appear to work by changing the way appetite is regulated in the brain, rather than altering basic metabolism.

Elizabeth Speliotes, a genetic epidemiologist at the University of Michigan and senior author, said: “Looking at obesity, we didn’t necessarily expect to see genes that work in the brain. In retrospect it’s not that surprising that appetite and feeding pathways have a big role.”

Prof Alistair Hall, a cardiologist at Leeds University, said the paper added to a growing recognition that, for some people, eating in moderation is genuinely more challenging, in the same way that some people find it more difficult to give up smoking or drinking.

“Some people are potentially more addicted to food,” he said. “They simply find it harder to suppress their appetite.”

The findings also reveal the existence of genetic variants that increase a person’s chances of being obese, but simultaneously protect against diabetes and heart disease, adding credibility to the idea that some people can be overweight and healthy.



Speliotes predicted that in future people could be genetically screened to assess whether their weight was likely to raise their risk of disease – and for a fraction of people, being overweight might not be linked to health problems. “There are almost definitely very healthy obese individuals,” she said. “And who cares about obesity if it’s not going to affect your health?”

Hall agreed: “This study is telling us that not everyone who is obese is necessarily heading for problems like diabetes and heart disease.”

The research, published in the journal Nature, analysed the genomes of 339,224 individuals and sifted through the data to pinpoint genes that had an effect on body mass index (BMI).

The analysis reinforces the idea that weight is influenced by a very large number of genes each making a small contribution. Even the 97 genes variants shown to have the most powerful effect together only explain about 3% of the variation in BMI across the population. The remaining 18% of variation in weight that the study accounts for is linked to rarer genes or ones that have a barely discernible impact. “No one gene is very powerful in its own right,” said Hall.

Cumulatively, though, the impact of genes is substantial. A person with 104 “high-risk” gene variants is on average 11kg heavier than someone with only 78 variants associated with weight gain, for instance. “That’s a really big deal,” said Speliotes.

She added that even those carrying a high number of “risk” variants could maintain a healthy weight by eating healthily and exercising, however. The researchers predict that the dramatic increase in the number of known genetic pathways linked to obesity will provide drug companies with new targets for developing drugs designed to slow metabolism or suppress appetite and ultimately improve treatments.

A second study, also published today in Nature and involving a further 220,000 people, shows that genetics has a role in determining shape as well as size. The paper locates tens of gene variants that predispose people to bulk up around the middle, which carries a greater risk of metabolic illnesses.

In 1993, 13% of men in Britain and 16% of women were obese, but by 2011 this had risen to 24% of men and 26% of women.

Scientists believe that in our evolutionary past, certain genes that slowed metabolism and boosted appetite would have been beneficial – the so-called “thrifty gene” hypothesis. While such variants would leave you with less energy for physical and mental exertion, storing energy in fat reserves would help tide you over during times of scarcity.

“We’ve been on the planet for the past five million years, but only had great food supplied for the past 100 years,” said Hall. “It’s not surprising that we’re not genetically ideally adapted to our environment today.”