Study sheds light on the role of genetics in the body weight

The obesity rate has been steadily climbing and so have scientific efforts to understand why. A new study, published in Nature Communications, takes a closer look at the genes behind body weight and how they might point toward future treatments for obesity.

For decades, scientists have sought a single “obesity gene.” However, research now indicates that obesity is a complex trait, shaped by the combined effects of many genes, each with a small contribution, and influenced by lifestyle and environment. To measure it, researchers use body mass index (BMI), a simple ratio of height and weight that categorizes individuals from underweight to obese. Although BMI does not take into account factors such as muscle mass, age, or body type, it serves as a useful initial indicator of whether a person’s weight is within a healthy range.

The new study analyzed BMI data from 204,747 Estonian participants, excluding extreme outliers and focusing on young adults. An author of the study, functional genomics researcher Erik Abner, explained that the analysis focused on the youngest reported body mass index (BMI) of gene donors, as genetic influences tend to manifest most clearly at a young age.

“As people grow older, environmental factors, such as diet, accompanying illnesses, and lifestyle, begin to play a greater role,” he added.

The research team performed a genome-wide association study (GWAS), scanning millions of genetic markers to identify variants linked to body weight. By using Estonia’s population-specific genetic reference data, they were able to detect subtle effects that global studies often overlook.

Obesity is not just about calories or willpower

Although Estonians are genetically quite similar to other Europeans, the study revealed unique traits that play a significant role in appetite and body weight. According to Abner, this suggests that region-specific genetic variations may influence both health risks and responses to treatment.

Researchers identified a genetic variant in the MC4R gene associated with lower body mass index (BMI), found in 3.5% of Estonians. According to Erik Abner, this means that individuals with this variant tend to have a lower appetite, and consequently, lower body weight.

Conversely, a variant of the POMC gene was found in 0.85% of Estonians. Although rarer, it is linked to significantly higher body weight. Carriers of this variant produce fewer appetite-suppressing hormones in the brain, leading to a slower onset of satiety and increased hunger. For the average Estonian woman, this variant increases weight by approximately three kilograms, and for men, by just over one kilogram.

Interestingly, Abner points out that a similar variant has been identified in Labrador Retrievers. Studies show it increases appetite and makes treats especially motivating as rewards—one reason why retrievers are more prone to obesity than other dog breeds. Based on this canine example, it’s reasonable to assume that the variant found in Estonians similarly boosts appetite and reduces satiety in humans.

The study also revealed that genes related to the nervous system and behavior play a key role in shaping BMI. For the first time, researchers have found a link between body weight and the ADGRL3 and PTPRT genes—both of which influence brain function and neural communication.

These genes have previously been associated with attention disorders and learning ability, but now appear to affect body weight as well. Abner suggests their mechanism may involve the regulation of appetite hormones, making them potential targets for future anti-obesity drugs.

Future studies

According to the researchers, studies like this bring us closer to personalized medical solutions. The findings help explain why some individuals have a stronger genetic predisposition to weight gain and why the same diet or treatment doesn’t work equally for everyone. The identified genes offer new targets for developing anti-obesity medications and may eventually allow treatments to be tailored to a person’s genetic profile.

Currently, the research team is launching a follow-up study to investigate how modern obesity medications, such as those containing semaglutide, affect individuals with these specific genetic variants. Since semaglutide influences appetite-regulating hormones, its effectiveness may vary depending on the genetic makeup of the patient. This knowledge could help doctors make more precise, genetically informed treatment decisions in the future.