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Mutation in single gene could cause some people to be 2.5 stone heavier by age 18, Cambridge and Bristol researchers find

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A mutation in a single gene could be responsible for some people being two-and-a-half stone heavier than they otherwise would be by the age of 18, University of Cambridge research suggests.

One in 340 people - about 200,000 people in the UK - are believed to carry this mutation, which is responsible for sending a signal that means their brains think they are starving and need to eat.

Prof Sir Stephen O’Rahilly. Picture: Keith Heppell
Prof Sir Stephen O’Rahilly. Picture: Keith Heppell

Prof Sir Stephen O’Rahilly, from the University of Cambridge and one of the authors of the study, said: “Parents of obese children are often blamed for poor parenting and not all children obtain appropriate professional help.

“Our findings show that weight gain in childhood due to a single gene disorder is not uncommon.

“This should encourage a more compassionate and rational approach to overweight children and their families – including genetic analysis in all seriously obese children.”

The study was led by scientists at the MRC Metabolic Diseases Unit, part of the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge, along with the MRC Integrative Epidemiology Unit at the University of Bristol.

They examined data from a random sample of around 6,000 people born in Bristol in 1990-91 involved in the unique Children of the 90s health study, which recruited about 80 per cent of births in a specific region of the South West, and has continued to follow them.

The University of Bristol study is one of the most representative and comprehensive research projects of its kind.

While it has long been known that obesity tends to run in families, it was only about 20 years ago that scientists found changes in certain genes can have significant impacts on weight, even from early childhood.

For the new research, the Cambridge and Bristol researchers examined the Melanocortin 4 Receptor (MC4R) gene, which makes a protein produced in the brain that sends signals to our appetite centres, telling them how much fat we have stored.

Prof Sir Stephen O’Rahilly. Picture: Keith Heppell
Prof Sir Stephen O’Rahilly. Picture: Keith Heppell

When the MC4R gene does not work properly, it means our brains think we have lower fat stores than we do, prompting the carrier to feel the need to eat.

The researchers found people with this mutation were more likely to have a greater weight from early childhood. By 18, they were on average 17kg (37lbs or 2.5 stone) heavier, with the majority of this excess weight likely to be fat.

The authors of the study, published in Nature Medicine, examined the MC4R gene in all 6,000 people. Whenever they found a mutation, they studied the functional effects in the laboratory, giving rise to the best estimates so far of the frequency and impact of MC4R mutations on people’s weight and body fat.

Dr Kaitlin Wade, from the University of Bristol’s MRC Integrated Epidemiology Unit and an author on the paper, added: “Work like this is really made possible as a result of the amazing properties presented by a study like Children of the 90s.

“Having biological samples for sequencing and rich life course data within a representative population sample is critical to allow new understanding and deep characterisation of important biological genetic effects like these.”

Another study author, Prof Nic Timpson, Children of the 90s’ principal investigator, added: “This work helps to recalibrate our understanding of the frequency and functional impact of rare MC4R mutations and will help to shape the future management of this important health factor – we extend our thanks to the participants of the Children of the 90s.”

Knowledge of the brain pathways controlled by MC4R could, in the future, enable the design of drugs that bypass the signalling blockade, which may help people maintain a healthy weight.

While considered a significant example, MC4R is just one gene of many that affect our weight. The growth of genetic sequencing is likely to lead us to discover more examples.

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