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Physical Inactivity, Poor Sleep Can Amplify Genetic Risk of Obesity

NEW YORK (GenomeWeb) – Not being physically active and not getting enough sleep can amplify a person's chances of becoming obese if they are already at genetic risk of developing the condition, according to a new study.

Previous work based on self reports has suggested as much, but researchers from the University of Exeter Medical School have now combined data from wrist-worn accelerometers with genetic data gathered by the UK Biobank effort, finding evidence of gene-activity interactions.

"We wanted to find out if obesity-related genes and activity level have an interactive effect on obesity risk — if there is a 'double-whammy' effect of being both at genetic risk and physically inactive, beyond the additive effect of these factors," Andrew Wood, a postdoctoral researcher at Exeter, said in a statement. Wood presented the results at the American Society of Human Genetics meeting in Orlando, Fla. this morning.

The researchers used data on 120,000 individuals from the first release of the UK Biobank study. That project is collecting DNA, medical, and lifestyle information on 500,000 people to study the genetic and environmental sources of disease.

Of those 120,000 participants, Wood and his colleagues had accelerometer data on 19,229. From that data, the researchers could gauge physical activity and sleep, including total activity, bouted activity, sleep duration, and sleep efficiency. They also used self-reported measures of physical activity and sleep that had been collected from 109,142 people.

At the same time, they examined the participants' genetic data for variants linked to body-mass index and assessed them on a 76-variant genetic risk score for obesity.

From within this data, the researchers uncovered evidence of gene-activity interactions. They found that the effect of the genetic risk score for obesity appeared to be larger in the people who reported low levels of physical activity.

They uncovered 10 further alleles linked to increased BMI that were associated with a nearly 8 pound increase in weight in people five feet eight inches tall who weren't physically active, while those alleles were associated with about a 6-pound weight increase in people of the same height, but who were more active.

However, Wood and his colleagues also found a weak interaction in their negative controls, which suggested to them that confounding factors other than physical activity also have an influence on people's genetic risk of obesity.

They also found an interaction between the genetic risk score for obesity and sleep efficiency, with a stronger BMI effect in people who didn't sleep as well.

The researchers said that their findings are consistent with previous reports that have indicated that low levels of physical activity and sleep magnify the genetic risk of obesity.

They are now examining whether these findings vary between men and women and whether the type of activity — for instance, consistent moderate activity or bursts of intense exercise — has differing effects.

"We hope these findings will inform clinicians who help people lose or maintain their weight, and contribute to the understanding that obesity is complex and its prevention may look different for different people," Exeter's Timothy Frayling said in a statement. "Ultimately, with further research, we may have the scope to personalize obesity interventions."