A clutch of genes that raise the risk of obesity has been discovered by British researchers, offering fresh insight into the role the brain plays in overeating.
People who inherit the six new gene variants weigh on average 1.5 to 2kg (3.3 to 4.4lbs) more than those with none of them, according to a study of 90,000 volunteers.
Five of the six genes are active in the brain, where they are linked to behaviour and nerve development, rather than how our bodies process the food we eat and store fat.
"It might seem remarkable that it is the brain that is most commonly influenced by genetic variation in obesity, rather than fat tissue or digestive processes, but today almost all those we have uncovered are likely to influence brain function," said Inês Barros at the Wellcome Trust's Sanger Centre in Cambridge.
The findings, published in Nature Genetics, suggest that some people are effectively hardwired to overeat, through genes that control appetite, satiety and how many calories they burn.
The research was carried out as part of an international project involving scientists from 60 institutions. To find the gene variants, scientists analysed the genetic make-up of 32,387 Europeans and confirmed that the variants cause an increase in body mass index (BMI) by checking for them in 50,000 individuals.
One of the differences the team found in heavier people was a loss of 45,000 "letters" of genetic code. The missing DNA is thought to affect the behaviour of a neighbouring gene called NEGR1, which regulates nerve growth in the developing brain.
Obesity rates in Britain have risen nearly fourfold in the past 25 years, making it the most obese country in Europe. More than one in five men and a quarter of women in Britain are now clinically obese. Each year an estimated 30,000 people in England alone die prematurely from obesity-related conditions such as diabetes, heart disease and cancer.
Studies in twins suggest that genetics account for 40-70% of the difference in people's bodyweight.
Some of the new obesity genes appear to spring into action at different times of life. "In younger children aged five to ten, we found that with three of the genes the children were already heavier at that young age, and with the other three genes, we saw that there was no effect on children. For those, we only saw an effect in much older individuals," said Goncalo Abecasis, a co-author on the study from the University of Michigan.
"It's different if you know that overeating is about biology, and it takes a major effort to overcome that biology," added Cristen Willer, also at Michigan. "Clearly this suggests that some aspects of eating behaiour may be something you are born with."
Unravelling the genetic factors that contribute to obesity will help scientists understand the crucial biological pathways that drive the condition and so improve their chances of developing drugs to combat it.
Last year, scientists reported that people who inherited a particular form of a gene called FTO were 70% more likely to be obese than those who did not. Inheriting this and another gene called MC4R increased body weight by 4-5kg (8.8-11lbs). Both genes are thought to influence appetite and how much energy the body uses.
