CHOP teams finds another genetic clue to childhood obesity

Researchers at the Children’s Hospital of Philadelphia say they’ve uncovered the next clue in an emerging map of the genetic underpinnings of childhood obesity.

The team used a research approach that’s just 5 or 6 years old to scan the DNA of two groups of children — obese kids and a control group of leaner young people.

It’s the first time a genome-wide association study looked for variants linked to common childhood obesity, although the technique has been used for adults and for rare kinds of childhood obesity.

The work isolated mutations on, or nearby, two genes never before linked to obesity in kids, said study author Struan Grant, associate director in the Children’s Hospital’s Center for Applied Genomics.

“It’s too early to use these variants to predict your genetic risk for childhood obesity if you are thinking of your child,” Grant said. “However, we would say that it’s clearly not just entirely lifestyle driven. The trait definitely has a genetic component to it.”

During a conference call, he explained the team’s confidence that the new variants are associated with childhood obesity.

“Effectively what we do when we do genome-wide association studies is that we get a strong signal, but we don’t believe for a moment that that is the causative variant. Rather, it is a tag,” Grant said. “So it’s basically telling us that something in the near vicinity, in the very close vicinity, is an underlying causative variant contributing to the susceptibility to the disease.”

Next task is to pinpoint function

Grant hopes to launch a new study to pinpoint the function of the newly identified genes.

“Based on the very little knowledge that’s already known about them, they appear to operate in the gut and in the intestine,” he said. “So if I was to try to figure out the mechanism of these very robust signals, I would first look in the gut.”

The study also confirmed that several genes already linked to adult obesity are associated with obesity in children.

Genetic epidemiologist Ruth Loos, who directs the Genetics of Obesity and Related Metabolic Traits program at Mount Sinai School of Medicine in New York, said it’s fascinating to learn that these formerly identified gene variants are operating early in life.

“Environment remains an important part of body weight regulation, but it seems that these genes put individuals on a certain track early on in life,” Loos said. For people who’ve inherited the obesity gene variants, she said, the usual suggestions to eat moderately and exercise would still apply. Those people with a genetic predisposition may need to be even more vigilant to maintain a healthy weight, she added..

Loos echoed Grant’s caution that the gene variants aren’t helpful in determining if a child will become obese.

For now, she says, the weights of a child’s parents are better predictors that weight reflects both environment and genetics.