Genetic Link to Weight and Obesity – Sanger Institute


Obesity is a state of positive energy balance and basically what that means is that there is excess energy consumed Compared to the amount of energy that we spend to get on with our daily lives And so this excess energy has to be stored in the form of fat It’s become a huge problem worldwide and it’s even more troubling because it’s increasing in younger children And at the moment in western countries about 20% of the adult population is obese And probably around 50% are obese or overweight The obesity epidemic is clearly the result of changes of lifestyle and environment However, there is a lot of evidence that genetics has a huge role to play And this evidence comes initially from family studies and particularly looking at twins But more obviously when people started finding mutations in genes that actually lead to very severe forms of childhood obesity This is the closest evidence you can ever get to that genes have an important role to play In this study we took 16,000 people And we wanted to investigate the effect of 500,000 genetic variants across the human genome And their effect on body weight, to find out whether there are particular variants That were associated with higher body weight than people who did not carry those particular variants But because we did so many tests we then had to go and validate our findings in additional samples And that’s when we then recruited up to 90,000 individuals And tested the same variants in those to see if we could confirm our findings In our study we found evidence for a genetic variant that was close to a gene called melanocortin-4 receptor That genetic variant having an association with increased body weight This variant actually doesn’t exist within a gene so it doesn’t actually disrupt the gene itself But we think it might be important in regulating the activity of that gene Melanocortin-4 receptor is a gene that codes for a protein that is a receptor in the brain And what that means is that this particular protein is responsible for telling the brain Essentially whether or not it should stop eating and increase energy expenditure So that the body can maintain a normal weight Melanocortin-4 receptor is a very important molecule In a very complex pathway of different genes that are involved in energy regulation and metabolism So I don’t think that we can say ‘this is the most important molecule’ There are many things that integrate together to maintain normal energy balance in humans And many we still don’t know what they are

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