Gene variant tied to time sitting, body mass index

Growing stem cells in the laboratory (© 2009 Andrei Tchernov)

A common genetic variant may increase the risk of a high body mass index by increasing the amount of time a person spends sitting, according to a new study.

"This is an exciting time in science especially with respect to understanding the genetic basis of disease. There has been an explosion in our knowledge of the genes involved in susceptibility to obesity," lead author Yann Klimentidis of the University of Arizona in Tucson told Reuters Health by phone.

For example, he said, genes "could modulate how hungry we get or how quickly we become full after eating, modulate how active we are, and some people can sit for hours on end without any problem, some cannot sit for more than a few minutes."

"Those things probably have some genetic underlying factors," he said.

Klimentidis and colleagues used two large, long-term studies involving more than 4,000 subjects each, known as the Framingham Heart Study and the Women's Health Initiative, to examine whether a common variant of a gene called FTO was related to self-reported time spent sitting.

Klimentidis said that of all genes researched so far, FTO gene has the biggest effect on body mass index (BMI), which is a ratio of weight to height.

In the Framingham Heart Study, the BMI-increasing FTO variant was more common among people who also reported spending more time sitting. The link between time spent sitting and BMI was strongest for people with more high-risk FTO gene variants, which suggests that "sedentary time" may have more affect on body mass for those who have those genes.

There was also a significant interaction in the Women's Health Initiative, but it seemed to go in the opposite direction, the authors report in the International Journal of Obesity.

Though we may model our level of activity on that of our parents because that's what we see growing up, we also inherit some predisposition to sitting - or not sitting - in our genes, Klimentidis said.

"Even deep among scientists, people underestimate the extent to which behavior is genetically controlled," he said.

"We still don't know how FTO increases BMI," Klimentidis said.

Understanding how newly identified genes interact with lifestyle factors will someday help take a genetic profile and determine which interventions will be most effective to maintain a healthy weight, he said.

"Maybe physical activity will really benefit me a lot, but for someone else with a different set of genes physical activity might not help them as much, they might have to do twice as much as me," Klimentidis said.

"As we learn about how the specific genes affect obesity we might learn more about biological mechanisms, and we can target those biological mechanisms through drugs," or through specific preventive measures, he said.

But so far, it is too soon to map everyone's genes looking for the high-BMI variant of the FTO gene, which is found in more than a quarter of people with European descent, he said.

"What we've learned is there are not a handful of genes that determine obesity, but hundreds of thousands of genes, each with very small effects," he said. "One gene tells a tiny part of the story."