Unhealthy food environments and sedentary lifestyles certainly contribute to obesity, but they can’t entirely explain weight gain. The latest research points to four new genes that could contribute to the most extreme cases of obesity in childhood.
By comparing the genomes of 1,509 children in the UK with severe obesity to 5,380 similar children of normal weight, an international team of researchers first identified a series of 29 genetic changes that distinguished the heavier children. Narrowing these differences down to those that influence obesity, they found nine genes strongly linked to early weight gain, five of which were known, and four of which are new.
The findings suggest that childhood obesity may be driven by different genetic factors than adult obesity, which points to potentially different ways to treat the two conditions. A rare variant in one of the newly identified genes, LEPR, appeared more frequently among the children who developed obesity early on, but another version of the same gene appeared in about six percent of the population. Understanding how subtle changes in this gene can push the body either toward obesity or normal weight could lead to new treatments that more precisely target some of the root causes of weight gain, say the researchers.
Some of the other newly identified genetic changes were more prevalent among the children, which hinted at the fact that how these genes interacted with other factors, including lifestyle behaviors such as physical activity or exposure to pollutants, for example, as well as other genes, might determine their contribution to weight gain.
“Some children will be obese because they have severe mutations, but our research indicates that some may have a combination of severe mutations and milder acting variants that in combination contribute to their obesity,” Sadaf Farooqi of the University of Cambridge, and one of the study’s co-authors said in a statement.
The findings are part of a larger research initiative called the UK10K project that will continue to study the genes of 1,000 severely obese children without well-known obesity-related gene mutations. Researchers hope that work will continue to identify new genetic variants behind some of the more severe cases of childhood obesity, which in turn will improve understanding of its biological drivers and even shed light on other, more common forms of weight gain as well.
The study is published in the journal Nature Genetics.