May 4, 2017

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Dr. Misa Graff

Physical activity can reduce the weight-gaining effects of the genetic variant that carries the greatest risk of obesity, according to a large, international study co-led by Misa Graff, PhD, research assistant professor of epidemiology at the UNC Gillings School of Global Public Health, and Tuomas Kilpeläinen, PhD, associate professor of human genetics at the University of Copenhagen (Denmark).

The study was published online April 27 in PLOS Genetics.

As people consume more calories and become less physically active, the world has witnessed an obesity epidemic. Not everyone is gaining weight, however.

Previous studies suggest that a person’s susceptibility to becoming obese can be reduced by physical activity.

To determine how physical activity and genetic variants related to obesity interact to affect weight gain, Graff and colleagues performed genome-wide interaction meta-analyses using more than 200,000 individuals.

The researchers categorized individuals as active or inactive, screened them for about 2.5 million genetic variants and correlated that data with physical indicators of obesity, including body mass index, waist circumference and waist-to-hip ratio.

Findings show that physical activity can reduce the weight-gaining effects of the strongest known genetic risk factor for obesity, the FTO gene, by about 30 percent. Accounting for physical activity also enabled the researchers to identify 11 novel genetic variants linked to obesity, suggesting that physical activity and other relevant environmental factors should be considered when looking for novel genes.

The meta-analyses confirmed previous findings that physical activity reduces the effect of the FTO gene. However, the underlying cause of this interaction is still unknown. Physical activity may affect other genes related to obesity, but to identify these smaller effects, researchers will require larger groups of subjects and highly precise measurements.

From a practical standpoint, the findings suggest that physical activity is still vital, even when obesity appears to be predetermined in one’s genes, and could be most beneficial for those who have the hardest time keeping weight off.

“Our study revealed 11 completely new obesity genes,” Graff noted, “suggesting that in future studies, accounting for physical activity and other important lifestyle factors could boost the search for new obesity genes. [In our study], participants self-reported their physical activity habits rather than being surveyed objectively. To identify more genes whose effects are either dampened or amplified by physical activity, we need to carry out larger studies with more accurate measurement of physical levels.”

Other Gillings School co-authors include Anne E. Justice, PhD, postdoctoral fellow, Kristin L. Young, PhD, research assistant professor, and Kari North, PhD, professor, all from the Department of Epidemiology; and professors Linda Adair, PhD, and Penny Gordon-Larsen, PhD, in the Department of Nutrition.

The research team included scholars from a number of universities in the United States and from at least 15 countries.


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Gillings School of Global Public Health contact: David Pesci, director of communications, (919) 962-2600 or dpesci@unc.edu

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