It is estimated that a quarter of adults in the United Kingdom are obese. In addition to obesity being strongly heritable, the increased availability and affordability of energy dense foods has contributed to this global public health problem. However obesity can sometimes be caused by disorders of single genes. The Melanocortin 4 receptor (MC4R) is a gene that works in the brain to influence both appetite and how fast energy is burned off in the body. People who have mutations that disrupt the function of even just one of the two copies of the MC4R are often obese from early childhood. MC4R is the most common single gene disorder responsible for obesity and although estimates of its frequency in the population have been made, we don’t know exactly how common it is. We also don’t know exactly what the chances of a person carrying one bad copy of the MC4R gene has of becoming obese or when during their life this would start to be noticeable. To address this we will identify carriers of significant MC4R mutations by carrying out sequencing of the gene on DNA samples collected from the ALSPAC G1 cohort and by using our knowledge and lab testing to determine which mutations actually do impair the function of MC4R and which are just variations of normal

This work will tell us a) what the frequency of significant MC4R mutations are in a relatively unselected UK population b) how often such mutations lead to obesity

There are now trials ongoing of specific treatments for obesity associated with MC4R mutations. If those trials prove positive then it will be very important to know how many patients in the UK might benefit and to set up systems to identify MC4R deficient children