Study Identified Rare Genetic Mutations That Protect People From Weight Gain

Losing weight can be a very painful and difficult process for some people. Obesity and metabolic disorders make the entire weight loss process much more complicated. Even performing a readjustment in the diet and inserting the practice of exercises in the daily life, losing weight may not be a simple task.

Genetics can play a big role in both helping and hindering weight loss or gain. Now, a large study of 645,626 people in the US, UK and Mexico has found a variant of a rare gene that appears to provide “substantial protection” against weight gain .


Approximately one in 2,500 people appear to have this specific mutation in the gene called GPR75. Those in this rare group of people have a lower body weight, in addition to being 54% less likely to be obese.

The study results are consistent across multiple ancestors, environmental exposures, and genetic origins. And they suggest that GPR75 is one of several genes involved in weight gain.

This study was based on a relatively new technique called complete exome sequencing. It can help researchers find mutations in certain genes and thus reveal their effects.

The exome, rather than sequencing each of the genes in the human genome, focuses only on exons, which make up about 1% of all DNA. Exons are the pieces that are instructions for proteins. This means that when the entire subset is sequenced, it is possible to identify changes in the protein encoded regions of any gene. Such variations are quite rare, but when they are found they self-identify.

“The principles of discovery exemplified in the study go beyond controlling body weight and obesity. Sequencing the human exome at scale is likely to become an increasingly important entry point for discovering mechanistic insights into mammalian biology,” wrote metabolic disease researchers Giles Yeo and Stephen O’Rahilly, who were not. involved in the study.


The team was able to identify a total of 16 genes that were linked to mutations in a person’s exon and body mass. Four of these genes had already been found in previous studies of weight gain . They are known to influence appetite. This shows that the authors of this study are on the right track.

Among all the mutations, the GPR75 gene had the greatest effect on a person’s body mass index. People who had this mutation weighed, on average, 5.3 pounds lighter than the rest.

“Although it is not clear whether the thinness of these animals is due to effects on energy intake, expenditure or both, this study establishes that GPR75 is involved in the control of energy balance and that the inhibition of its signaling can result in a loss of body weight,” wrote Yeo and O’Rahilly.