Walking more may lower risk for obesity among adults at high genetic risk
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Key takeaways:
- Increased polygenic risk score and walking less were both associated with higher risk for developing obesity.
- Adults at high genetic risk may reduce their obesity risk by walking more steps per day.
People with a higher genetic risk for obesity may need to perform more physical activity to prevent obesity, according to findings published in JAMA Network Open.
In an analysis of data from the NIH’s All of Us Research Program, researchers found that people with a polygenic risk score for obesity in the 75th percentile need to walk 2,280 more steps per day to have the same obesity risk as those with a polygenic risk score in the 50th percentile, whereas adults in the 25th percentile for polygenic risk score can walk 3,660 fewer steps per day before having the same obesity risk as those in the 50th percentile.
“Current physical activity guidelines take a ‘one-size-fits-all’ approach to activity recommendations, which may not be sufficient for individuals at high genetic risk of obesity,” Evan L. Brittain, MD, MSCI, associate professor of medicine at Vanderbilt University Medical Center, and Douglas M. Ruderfer, PhD, director of the Center for Digital Genomic Medicine and associate professor of medicine, biomedical informatics and psychiatry and behavioral sciences at Vanderbilt University Medical Center, told Healio. “Our findings suggest that physical activity recommendations can be adjusted based on genetic risk providing individualized guidance to reduce the risk of obesity.”
Brittain, Ruderfer and colleagues obtained data from 3,051 All of Us Research Program participants of European ancestry with a BMI of less than 30 kg/m2 at the start of the study who enrolled from May 1, 2018, to July 1, 2022 (median age, 52.7 years; 73% women). Daily step counts were collected from personal tracking devices. A polygenic risk score for BMI was assigned to each participant and the study group was divided into quartiles based on polygenic risk score. The primary outcome was incident obesity, defined as adults whose BMI increased to 30 kg/m2 or higher at least 6 months after monitoring began.
During a median follow-up of 5.4 years, 13% of adults in the lowest polygenic risk score quartile developed obesity and 43% in the highest quartile developed obesity.
In a Cox proportional hazards regression model, obesity risk was stratified so that a 50th percentile polygenic risk score was equivalent to an HR of 1 for developing obesity. In the model, adults in the 75th percentile for polygenic risk score had an 81% higher risk for obesity than those in the 25th percentile (HR = 1.81; 95% CI, 1.59-2.05). Adults in the 75th percentile for median daily step count had a 43% lower risk for obesity than those in the 25th percentile for daily steps (HR = 0.57; 95% CI, 0.49-0.67).
In an analysis stratifying for baseline BMI, adults in the 75th percentile for obesity need to walk an additional 3,460 steps per day with a baseline BMI of 22 kg/m2, an additional 4,430 steps per day with a baseline BMI of 24 kg/m2, an additional 5,380 steps per day with a baseline BMI of 26 kg/m2, and an additional 6,350 steps per day with a baseline BMI of 28 kg/m2 to achieve the same obesity risk as adults in the 25th percentile for polygenic risk score.
The cumulative incidence for obesity at 1 year was 2.9% for adults in the 25th percentile for polygenic risk score, 3.9% for the 50th percentile and 5.2% for the 75th percentile. At 5 years, the cumulative incidence for obesity was 18.5% for the 25th percentile for polygenic risk score, 24.3% for the 50th percentile and 30.9% for the 75th percentile.
Brittain and Ruderfer said they were pleased to see that adults with any level of genetic risk for obesity could modify their level of activity to try and better prevent the disease.
“Our results needs to be demonstrated in a more representative population, and we hope to show that providing these genetically informed activity recommendations can reduce likelihood of obesity,” Brittain and Ruderfer said.
For more information:
Evan L. Brittain, MD, MSCI, can be reached at evan.brittain@vumc.org.
Douglas M. Ruderfer, PhD, can be reached at douglas.ruderfer@vumc.org.
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