A six-month clinical trial found that individuals with a high genetic risk for obesity benefited as much from dietary coaching as those with low genetic risk, according to a study published on Jul. 17 in Nature Communications.
The randomized controlled trial involved participants from the FinnGen study who were overweight or mildly obese adults without diabetes. These participants had body mass index polygenic scores (BMI PS) within either the highest or lowest 5% of the genetic risk distribution. A total of 223 participants, with a mean age of 51 years and 75% women, were randomly assigned to receive structured dietary coaching or to a control group without nutritional coaching for six months.
At baseline, those with the highest genetic predisposition had an average BMI that was 3.0 kg/m² higher than those with the lowest risk. After six months, both groups receiving dietary coaching reduced their BMI by an average of 1.51 kg/m², while there was virtually no change in the control group. The researchers reported no statistically significant interaction between BMI PS and dietary treatment effectiveness: "individuals with a high genetic risk for obesity lost a similar amount of BMI to those with low genetic risk." However, they cautioned that modest effects could not be ruled out due to sample size limitations.
Exploratory analyses indicated that consistent logging of meals and physical activity was associated with greater reductions in BMI, but this accounted for only a small proportion of overall weight loss. The study also examined cardiometabolic health outcomes; compared to controls, those receiving dietary intervention experienced greater reductions in total and LDL cholesterol, while changes in other metabolic markers were less clear. Genetic predisposition did not appear to meaningfully influence these exploratory outcomes.
The findings align with previous research using genome-wide polygenic scores showing little evidence that genetic predisposition alters responses to behavioral weight-loss interventions, but differ from bariatric surgery studies where lower genetic risk is linked to more long-term weight loss.
Researchers noted several limitations: small sample size may have limited detection of subtle interactions; results may not generalize beyond overweight or mildly obese adults without diabetes; most participants were women; and actual energy intake was not measured in detail during the intervention period. They concluded that larger studies using more predictive polygenic scores are needed across diverse populations.
