Scientists find ‘game-changing’ rare gene variants that protect against obesity after huge DNA study

Research suggests people with rare genetic mutations could be 54 per cent less likely to develop obesity

The World Health Organisation found in 2016 that more than 650 million people were living with obesity worldwide (Shutterstock / kurhan)

Scientists have identified a group of rare gene variants that help to protect people against obesity, following one of the most comprehensive studies to date of the genetics behind the condition.

Researchers from the Regeneron Genetics Centre analysed genetic data from more than 640,000 people from Mexico, the US and the UK to find new insights into the genetic basis of obesity.

The study, published in the journal Science, found that people with rare genetic mutations in the GPR75 gene had a 54 per cent reduced risk of obesity and on average tended to weigh about 12 pounds less than those without them.

The findings could go some way to explaining why some people are less susceptible to putting on weight than others, as the study found that just one in every 3,000 people analysed had the protective mutations.

“Discovering protective genetic superpowers, such as in GPR75, provides hope in combating global health challenges as complex and prevalent as obesity,” George D Yancopoulos, president and chief scientific officer at Regeneron, said in a statement.

The discovery could be used to develop genetics-driven drugs to help patients struggling with obesity, as scientists at Regeneron are said to be pursuing multiple therapeutic approaches to targeting the GPR75 gene.

In order to test how GPR75 affects weight gain, the research team genetically engineered mice to not have a working copy of the gene and found that the animals gained 44 per cent less weight than mice without the mutation when fed the same high-fat diet.

As of 2016, more than 1.9 billion adults are thought to be overweight, with more than 650 million of these people obese, and worldwide obesity has nearly tripled since 1975, according to the World Health Organisation.

Christopher Still, director for the Geisinger Obesity Research Institute at the Geisinger Medical Centre in Pennsylvania, said that the discovery was “potentially game-changing” and could help to improve the lives of millions of people.

“While the behavioral and environmental ties to obesity are well understood, the discovery of GPR75 helps us put the puzzle pieces together to better understand the influence of genetics,” Mr Still said.

“Further studies and evaluation are needed to determine if reducing weight in this manner can also lower the risk of conditions commonly associated with high BMI, such as heart disease, diabetes, high blood pressure and fatty liver disease.”

The study was conducted in collaboration with Geisinger Health System, New York Medical College, the Nuffield Department of Population Health at the University of Oxford and the National Autonomous University of Mexico (UNAM).

Researchers collected genetic data for the study from the Mexico City Prospective Study, Geisinger's MyCode Community Health Initiative and the UK Biobank.