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The daily step count needed to reduce the risk of obesity may be largely dependent on genetics, a retrospective cohort study indicated.

Among U.S. adults without obesity in the All of Us Research Program, incidence of obesity over a median follow-up of 5.4 years was 13% for those in the lowest quartile of BMI polygenic risk score (PRS), but reached 43% for those in the highest quartile. Higher PRS and lower daily step counts were each independently associated with an increased risk for obesity, reported Evan Brittain, MD, MSc, of Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues.

In order to have an obesity risk comparable to that of individuals in the 50th percentile of PRS, those with a PRS in the 75th percentile would need to walk an average of 2,280 more steps per day, while people in the 25th percentile could walk 3,660 fewer steps, the group detailed in .

"Your genetics are not your destiny with regards to obesity risk," Brittain told MedPage Today. "We showed that even high genetic risk for obesity can be overcome with higher levels of activity, which I think is an empowering message."

He added that most guidelines do not account for genetic risk of disease and often tend toward a "one size fits all" approach. "This is true for physical activity guidelines as well," he said. "One of the central messages [of this study] is that risk for obesity and how much activity is needed to prevent it varies dramatically across the genetic spectrum. Therefore, public health guidelines likely underestimate the amount of activity needed to prevent obesity in individuals with higher genetic risk."

Participants' BMI at baseline also played a role, said Brittain, who added that together the findings move the field closer toward a time when activity recommendations that account for genetic background can be personalized.

"Patients and their doctors are increasingly gaining access to genetic information that may have clinical importance. In the future, I suspect doctors will be able to take advantage of this information to provide more personalized 'prescriptions' for activity to prevent obesity and other chronic diseases associated with sedentary behavior," he explained.

But until then, doctors should keep in mind that individuals with high genetic risk or those with a BMI closer to 30 likely need to walk more than the typical target of 8,000 to 10,000 steps per day to reduce obesity risk.

Data for the current analysis included 3,051 individuals enrolled in the All of Us Research Program from 2018 to 2022. These people already owned a Fitbit activity tracker that clocked daily step counts and had available genome sequencing, with PRS quantified from a large-scale genome-wide association study of BMI. People who had fewer than 100 daily steps or more than 45,000 were excluded.

At baseline, participants had a median age of 52.7 years, 73% were women, and 95% were white -- the lack of diversity due to enrollment of people of European ancestry was a noted limitation of the study. Their median daily step count was 8,326 steps.

Across PRS quartiles, the median baseline BMI increased slightly from the lowest to highest quartile (24, 24.5, 25, and 25.5) while median daily steps decreased (8,599, 8,374, 8,222, and 8,115, respectively).

People who fell into the 75th percentile for PRS had an 81% increased risk for obesity over the study period compared to those in the 25th percentile (HR 1.81, 95% CI 1.59-2.05), while participants in the 75th percentile for step count (median 11,300 per day) had a 43% reduction in obesity risk compared with those in the 25th percentile (6,500 per day; HR 0.57, 95% CI 0.49-0.67).

When stratified by baseline BMI, people in the 75th percentile of PRS would have to walk up to 6,350 more steps per day in order to have a comparable obesity risk as those in the 25th percentile:

• BMI 22: 3,460 more steps
• BMI 24: 4,430 more steps
• BMI 26: 5,380 more steps
• BMI 28: 6,350 more steps

Limitations cited by Brittain and colleagues included that the cohort only included individuals who owned a fitness tracking device and had used them long-term (median 5 years or more), which may not be reflective of the greater population, and that dietary patterns were not available for assessment. Also, when determining genetic obesity risk, the researchers simplified this factor to be specific to increased BMI and didn't account for other factors like cardiometabolic conditions. The widespread availability of PRS quantification may also prove to be a barrier for determining person-specific step-count goals for mitigating obesity risk.

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