Diet helps people lose weight regardless of genetic obesity risk

By Dr. Liji Thomas, MDReviewed by Lauren HardakerJul 17 2026

A six-month clinical trial found that people with a high genetic risk for obesity benefited just as much from dietary coaching as those with low genetic risk, challenging the idea that DNA determines weight-loss success.

Study: Dietary intervention and BMI reduction in individuals at the extremes of genetic predisposition to higher BMI: a randomized controlled trial. Image credit: Lightspring/Shutterstock.com

A randomized controlled trial published in the journal Nature Communications found that people with a high genetic predisposition to obesity lost just as much weight from a six-month dietary intervention as those with low genetic risk.

Do genetics influence weight loss?

Experts estimate that more than half of the world's adult population will be overweight or obese by 2035, making obesity one of the most pressing public health challenges worldwide. Excess body weight increases the risk of numerous chronic conditions, including cardiovascular disease, type 2 diabetes, kidney disease and certain cancers, contributing to premature death.

Although lifestyle factors such as diet and physical activity play a major role in body weight, genetics also strongly influence an individual's susceptibility to obesity. Twin and family studies estimate that genetic factors account for between 23% and 90% of differences in body mass index (BMI), with genetic influences appearing to be stronger during childhood than adulthood.

Rather than being driven by a single gene, obesity risk reflects the combined effects of thousands of genetic variants. Researchers can combine these variants into a polygenic score (PS) to estimate an individual's inherited predisposition to obesity. While current BMI polygenic scores explain only about 8.4% of differences in BMI, far less than the heritability estimated from twin and family studies, they can still identify people at substantially different levels of genetic risk. For example, a UK Biobank study found that individuals in the highest 10% of BMI polygenic scores had a 25-fold greater risk of severe obesity than those in the lowest 10%.

Dietary interventions remain the first-line approach for weight management and typically produce average weight losses of 5–8.5 kg during the first six months of reduced-energy diets. However, it has remained unclear whether people with a higher genetic predisposition to obesity respond differently to these interventions. Previous studies have produced mixed findings: most research using genome-wide polygenic scores has found little evidence that genetic risk affects total weight loss, although one behavioural intervention study reported that individuals with higher genetic risk lost weight at a slightly slower rate.

To address these uncertainties, the current study prospectively examined whether people at the highest and lowest extremes of genetic risk for obesity differed in their response to a structured dietary intervention.

Comparing dietary response across genetic risk groups

Researchers conducted the GENEROOS randomized controlled trial involving participants from a subset of the FinnGen study that had already been genotyped. The participants were overweight or mildly obese adults without diabetes whose BMI PS fell within either the highest or lowest 5% of the genetic risk distribution.

The study included a total of 223 participants with a mean age of 51 years, 75% being women. The mean BMI was 30.3 kg/m² and they were randomly assigned to receive either structured dietary coaching or to a control group that received no nutritional coaching for six months. The primary outcome was change in BMI.

Diet reduced BMI regardless of genetic predisposition

At the start of the study, participants with the highest genetic predisposition to obesity already had a substantially higher BMI than those with the lowest genetic risk, with an average difference of 3.0 kg/m².

Despite this difference, both groups responded similarly to the dietary intervention. After six months, participants receiving dietary coaching reduced their BMI by an average of 1.51 kg/m², while the control group showed virtually no change. Although this reduction was meaningful, it represented only about half of the baseline BMI difference between the high- and low-genetic-risk groups.

When the researchers examined whether genetic predisposition influenced the effectiveness of the intervention, they found no statistically significant interaction between BMI PS and dietary treatment. In other words, individuals with a high genetic risk for obesity lost a similar amount of BMI to those with low genetic risk. However, the researchers cautioned that the study was not large enough to rule out more modest genetic effects on dietary response.

Additional exploratory analyses suggested that participants who logged their meals and physical activity more consistently tended to achieve greater reductions in BMI. However, the relatively small effect sizes indicated that adherence to logging accounted for only a small proportion of the overall weight loss.

The researchers also conducted non-prespecified exploratory analyses of cardiometabolic health. Compared with the control group, participants receiving the dietary intervention experienced greater reductions in total and LDL cholesterol, while changes in triglycerides, HDL cholesterol, glucose and HbA1c were less conclusive. Genetic risk also did not appear to meaningfully influence these exploratory outcomes.

Overall, the findings are consistent with previous studies using genome-wide BMI PS, which have generally found little evidence that genetic predisposition alters the effectiveness of dietary or behavioural weight-loss interventions. However, they differ from studies of bariatric surgery, where lower genetic risk has been associated with greater long-term weight loss. The researchers suggest that the much larger anatomical and metabolic changes produced by bariatric surgery, compared with dietary intervention alone, may make genetic influences easier to detect.

Study population limits broader application of findings

The researchers caution that several limitations should be considered when interpreting the findings. Although the study found no evidence that genetic predisposition influenced response to the dietary intervention, the relatively small sample size may have limited its ability to detect more subtle interactions between genetic risk and weight loss. The study population also consisted predominantly of women, although sex itself did not predict changes in BMI.

The findings may not apply to all populations, as the intervention lasted only six months and included only overweight or mildly obese adults without diabetes. Participants also required a smartphone and sufficient engagement with a digital coaching programme, potentially limiting the generalizability of the results to broader populations.

Another limitation was that, although participants received individualized calorie targets, the researchers did not measure actual energy intake in detail. As a result, they could not determine precisely how changes in dietary behaviour contributed to the observed weight loss.

The researchers conclude that future studies should evaluate newer, more predictive BMI PS in larger and more diverse populations to determine whether these findings can be replicated and whether improved genetic risk scores could eventually help personalize dietary interventions.

Diet worked regardless of inherited obesity risk

The findings suggest that current genome-wide BMI PS do not substantially modify short-term BMI reduction during dietary intervention in this population. Although individuals with a high genetic predisposition had higher BMI at baseline, they responded similarly to dietary intervention as those with low genetic risk.

Larger studies are needed to determine whether more subtle effects of genetic susceptibility on weight-loss response exist, and whether current PS are useful in personalizing dietary interventions for weight reduction.

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