New research published today in Nature Medicine has found that one in every 340 people might carry a mutation in a single gene that makes them more likely to have a greater weight from early childhood. By 18 years of age, people who carry a disruptive mutation in the MC4R gene were, on average, 17 kg (37 lbs or 2.5 stone) heavier, with the majority of this excess weight likely to be mostly fat.
It has long been known that obesity tends to run in families, but it was not until about 20 years ago that scientists started to discover that changes in specific genes can have very large effects on our weight even from early childhood.
One of these genes, the Melanocortin 4 Receptor (MC4R) gene, makes a protein that is produced in the brain where it sends signals to our appetite centres, telling them how much fat we have stored. When the MC4R gene does not work properly, our brains think we have lower fat stores than we do, signaling that we are starving and need to eat.
The study looked at a random sample of around 6,000 participants born in Bristol in 1990-91, who were recruited to Children of the 90s, a health study based at the University of Bristol. As the Children of the 90s study managed to recruit around 80% of mothers during pregnancy, it is one of the most representative and comprehensive studies of its kind.
Based on the frequency of mutations in this study, it is possible that around 200,000 people in the UK could carry a substantial amount of additional fat because of mutations in MC4R.
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.
Professor Sir Stephen O’Rahilly (joint author)
Though the MC4R gene is a striking example, this is only one gene of many that affect our weight and there are likely to be further examples that emerge as genetic sequencing becomes more common. In the longer term, knowledge of the brain pathways controlled by MC4R should help in the design of drugs that bypass the signaling blockade and help restore people to a healthy weight.
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To find out more about the genetics of obesity, watch Sadaf Farooqui’s talk Skinny Genes.
To find out more about obesity and COVID19, watch Stephen O’Rahilly’s talk Why Does Obesity Make COVID19 More Dangerous?