For the study, the researchers analyzed gene variants and activity levels of the Old Order Amish in Lancaster County, Pa., and found that the obesity-related FTO gene had no effect on individuals who were the most physically active.
"Our results strongly suggest that the increased risk of obesity due to genetic susceptibility can be blunted through physical activity," the authors said.
Evadnie Rampersaud, M.S.P.H., Ph.D., then of the University of Maryland School of Medicine in Baltimore and now of the University of Miami, and colleagues analyzed DNA samples of 704 healthy Amish adults (average age 43.6, 53 percent men and 47 percent women) recruited from 2003 to 2007.
Participants also underwent a series of physiological tests, including a seven-day measurement of physical activity using an instrument known as an accelerometer.
A total of 54 percent of the men and 63.7 percent of the women were overweight, and 10.1 percent of the men and 30.5 percent of the women were obese.
In the genetic analysis, 26 single-nucleotide polymorphisms (SNPs, or changes in a single base letter of DNA) in the FTO gene were associated with BMI.
The researchers then divided participants into two groups based on their physical activity levels and assessed the relationship between BMI and the two strongest SNPs.
Both SNPs were associated with BMI only in individuals who had low physical activity scores for their age and sex; they had no effect on those with above-average physical activity scores.
"Activity levels in the 'high-activity' stratum were approximately 900 calories [860 calories for women and 980 calories for men] higher than in the 'low-activity' stratum, which, depending on body size, corresponds to about three to four hours of moderately intensive physical activity, such as brisk walking, house cleaning or gardening," the authors said.
"In conclusion, we have replicated the associations of common SNPs in the FTO gene with increased BMI and risk to obesity in the Old Order Amish," they added.
"Furthermore, we provide quantitative data to show that the weight increase resulting from the presence of these SNPs is much smaller and not statistically significant in subjects who are very physically active.
"This finding offers some clues to the mechanism by which FTO influences changes in BMI and may have important implications in targeting personalized lifestyle recommendations to prevent obesity in genetically susceptible individuals," Rampersaud added.
The study is published in the Sept. 8, 2008, issue of the Archives of Internal Medicine.