Genes associated with childhood obesity discovered

Many people who become overweight in adulthood may never have been overweight in childhood.

Although diet and physical activity influence whether children become overweight, researchers have now mapped the genetic predisposition to obesity.

In the new study, researchers identified 47 sites in our genome in which minor changes can influence whether a child grows up with normal weight or being overweight.

The discovery advances researchers’ knowledge on the risk of becoming overweight in childhood but also on the risk of having lifelong challenges with obesity and many related diseases such as type 2 diabetes and high blood pressure.

“We know much more about the factors that influence adults becoming overweight versus children. In this study, we also investigated whether the genes involved in childhood and adult obesity overlap,” explains Tarunveer Singh Ahluwalia, Senior Researcher, Steno Diabetes Center Copenhagen and Associate Professor, Department of Biology, University of Copenhagen and former researcher, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen and COPSAC, Herlev & Gentofte Hospital.

The research has been published in PLoS Genetics.

Genes associated with obesity may not be identical for children and adults

Tarunveer Singh Ahluwalia explains that studying children’s genetic predisposition to obesity is interesting for several reasons.

The genetic analysis has a lower risk of confounders, since factors other than genetics affect children much less than adults.

For example, adults are more likely than children to have other diseases or to be affected by medication, and this can make the genetic results more unclear because correcting the data is analytically challenging, especially when it involves multiple participating centres across the globe.

In addition, in studies examining genetic factors for obesity in children, some identified genes may be involved in childhood and not in adults – or vice versa.

For example, many genes are active in childhood but are turned off in adulthood as part of the gene regulation system, and variation in these genes might affect whether a child, but not an adult, becomes overweight.

“The transition from childhood to adulthood involves many changes during lifetime, and we can miss some underlying genetic factors for obesity that initiate during childhood if we only examine adults. We should therefore consider the genetic risk factors in childhood to understand the overall situation,” explains Tarunveer Singh Ahluwalia.

Data on 61,000 children from 41 studies representing European ancestry

In the current genetic discovery and meta-analysis study, the researchers used data involving 41 studies and a total of 61,111 children between 2 and 10 years of age.

The current study had data on children’s genetic markers and whether the children were overweight or obese. With bioinformatics methods they identified whether specific genetic markers correlated with an increased risk of being overweight. The 41 studies were used in two parts: 1) to identify the genetic variants affecting childhood obesity and 2) to validate these findings.

In 26 of the included studies, the researchers identified 47 genetic variants associated with an increased risk of being overweight as a child.

The children who had specific genetic markers at these sites in the genome were more likely to be overweight.

Then the researchers confirmed the findings from the 47 genomic sites in the 15 other participating studies.

Two previously unknown associations between genes and obesity

Two of the 25 genetic variants significantly associated with childhood obesity were previously unknown.

These two genes, NEDD4L and SLC45A3, had not been previously linked to an increased risk of being overweight, either as a child or as an adult.

Six of the genes were already known to be associated with an increased risk of obesity in adulthood.

The researchers also found that a subset of these childhood obesity genes was also associated with high body mass index in adulthood, risk of type 2 diabetes and high blood pressure in adulthood.

The results suggest that the biological processes underlying the genetic risk factors for childhood obesity largely, but not completely, overlap with those underlying adult obesity.

Monitoring children over time

Tarunveer Singh Ahluwalia says that the study may help to identify new targets for drug development to combat the genetic predisposition to obesity among children.

The study also advances researchers’ knowledge about the mechanisms involved when both children and adults become overweight.

By studying the effect of the genes identified, researchers can much better understand why the body’ gets out of balance when it accumulates more fat than is healthy.

“This opens up the possibility of linking the sites found on the genome with drugs that already target these genes to determine whether they can be used to treat people with obesity,” explains Tarunveer Singh Ahluwalia, who is also leading another study exploring genes underlying childhood blood pressure in a collaborative international setting similar to this. Tarunveer Singh Ahluwalia says that following up and combining the two studies would be interesting to further explore identified genes, mechanisms and new therapeutic targets to prepare for preventing metabolic diseases in children and later in adulthood.

Finally, the study is the first in a series that will monitor the children as they develop into adults and link this with their genetic background.

“We really need data that enable us to monitor children over time and into adulthood. This will give us insight into how genes affect the body over a lifetime. It may also help to identify whether some of these genes influence not only the development of obesity but also the development of various other diseases such as those involving the regulation of blood pressure and the development of type 2 diabetes. If we can identify these genes and understand how they work during childhood, we can use this knowledge to help children to change their lifestyle, perhaps much earlier in life, so that they counteract the risk of developing a lifelong illness,” says Tarunveer Singh Ahluwalia.