Diet can help you lose weight, regardless of genetic obesity risk

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

Study: Dietary intervention and BMI reduction in individuals with extreme genetic predisposition to high BMI: A randomized controlled trial. Image credit: Lightspring/Shutterstock.com

Randomized controlled trials published in journals nature communications They found that people with a high genetic predisposition to obesity lost just as much weight over a six-month dietary intervention as people with a low genetic risk.

Does genetics affect weight loss?

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

Although lifestyle factors such as diet and physical activity have a large impact on body weight, genetics also strongly influence an individual’s susceptibility to obesity. Twin and family studies estimate that 23% to 90% of differences in body mass index (BMI) are due to genetic factors, and genetic influences appear to be stronger in childhood than in adulthood.

Obesity risk is not caused by a single gene, but reflects the combined effects of thousands of genetic variants. Researchers can combine these variations into a polygenic score (PS) to estimate an individual’s genetic propensity to obesity. Although current BMI polygenic scores only explain about 8.4% of the variation in BMI, which is much lower than the heritability estimated from twin and family studies, they can still identify people with substantially different levels of genetic risk. For example, a UK Biobank study found that individuals in the top 10% of BMI polygenic scores had a 25 times higher risk of severe obesity than individuals in the bottom 10%.

Diet remains the first choice for weight management, and an average weight loss of 5 to 8.5 kg is typically seen during the first 6 months of a reduced-energy diet. However, it remains unclear whether people with a higher genetic predisposition to obesity respond differently to these interventions. Previous studies have yielded mixed results. Although most studies using genome-wide polygenic scores found little evidence that genetic risk influences total weight loss, one behavioral intervention study reported that people with higher genetic risk lost weight at a slightly slower rate.

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

Comparison of dietary responses between genetic risk groups

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

The study included a total of 223 participants with an average age of 51 years, and 75% were women. With an average BMI of 30.3 kg/m², they were randomly assigned to either receive structured dietary counseling or a control group that received no nutritional counseling for 6 months. The primary outcome was change in BMI.

Diet reduces BMI regardless of genetic predisposition

At the start of the study, participants with the highest genetic predisposition to obesity already had a significantly 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 who received the dietary guidance had an average decrease in BMI of 1.51 kg/m², while the control group saw virtually no change. Although this reduction was significant, it was only about half the difference in baseline BMI between the high and low genetic risk groups.

When the researchers examined whether genetic predisposition affected the effectiveness of the intervention, they found no statistically significant interaction between BMI PS and diet. In other words, people with a high genetic risk for obesity lost the same amount of BMI as people with a low genetic risk. However, the researchers cautioned that the study was not large enough to rule out milder genetic influences on dietary response.

Additional exploratory analyzes suggested that participants who more consistently recorded their diet and physical activity tended to achieve greater reductions in BMI. However, the relatively small effect size indicates that logging compliance accounts for a small proportion of overall weight loss.

The researchers also conducted an unspecified exploratory analysis of cardiometabolic health. Compared to the control group, participants who received the dietary intervention experienced significant reductions in total and LDL cholesterol, but changes in triglycerides, HDL cholesterol, glucose, and HbA1c were inconclusive. Genetic risk also did not appear to significantly influence these exploratory results.

Overall, this finding is consistent with previous studies using genome-wide BMI PS, which have generally found little evidence that genetic predisposition alters the effectiveness of dietary or behavioral weight loss interventions. However, this differs from bariatric surgery studies, which show that lower genetic risk is associated with greater long-term weight loss. The researchers suggest that genetic effects may be easier to detect because the anatomical and metabolic changes induced by bariatric surgery are much greater compared to dietary intervention alone.

Study population limits broad application of research results

The researchers cautioned that several limitations should be considered when interpreting the findings. Although this study found no evidence that genetic predisposition influences response to dietary intervention, the relatively small sample size may have limited the ability to detect more subtle interactions between genetic risk and weight loss. Although the study population was also primarily composed of women, gender itself did not predict changes in BMI.

The study results may not apply to all populations, as the intervention lasted only six months and included only overweight or mildly obese adults without diabetes. It also required participants to have a smartphone and sufficient engagement with the digital coaching program, which could limit the generalizability of the results to a broader population.

Another limitation was that although participants were given individual calorie targets, the researchers did not measure their actual energy intake in detail. As a result, it was not possible to determine exactly how changes in dietary behavior 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 results can be replicated and whether improvements in genetic risk scores will ultimately help personalize dietary interventions.