Researchers at the University of Tartu have uncovered new genetic links that help explain why some people gain weight more easily and why others struggle to feel full.
Erik Abner, a research fellow in functional genomics, and his co-authors studied genetic variants related to excess weight in Estonians. Using data from the Estonian Biobank, the team analyzed participants’ body mass index (BMI) and identified which gene variants were most strongly associated with traits such as being overweight or underweight.
“We identified over 200 different genes linked to overweight among Estonians,” Abner said.
He explained that when it comes to BMI, the influence is roughly split between genetics and environment. “If you grow up in an environment with limited access to food, a genetic predisposition to obesity might not show. But in a world where junk food is always within reach, those genes can activate very quickly,” he said.
The study also found that the influence of genetics is strongest at a younger age.
“Young people show clearer genetic differences because their lifestyle isn’t yet fully established,” Abner explained. As people age, other factors — such as physical activity, diet, stress, sleep and comorbidities — tend to play a bigger role.
Many of the genes identified in the study were not related to metabolism but to brain processes, such as hunger regulation and emotional eating. This suggests that weight gain may be more connected to how the brain functions and influences behavior, rather than simply how efficiently calories are burned.
“Satiety is controlled through the brain. Genes affect how we perceive food and how strong our appetite is. In other words, the brain directs us and influences both conscious and unconscious eating choices,” Abner said. For instance, seeing a cinnamon roll might trigger stronger or weaker hunger signals depending on one’s genetics.
While many weight-related gene variants are already known internationally, no such in-depth study had previously been conducted specifically on the Estonian population. “That was our goal — to understand which variants are present here, what they do and why,” Abner said.
More than 200 gene variants influencing body weight were found in Estonian biobank data. While most were already known, several entirely new variants were identified.
One of the most striking discoveries involved the POMC gene, which plays a role in regulating satiety. It helps send fullness signals to the brain. About 1 percent of Estonians carry a variant that disrupts this gene’s normal function. These individuals may not feel full even after eating, leading them to consume more food than others.
“When I eat a burger, my body signals my brain that I’ve consumed a lot of calories and can stop eating — maybe even feel a little heavy. But for people with this POMC variant, that feeling of fullness doesn’t come as easily,” Abner explained.
While previously only a few such cases had been identified globally, about 1 percent of Estonia’s population carries this gene variant. It’s especially common in Estonia, Latvia and Lithuania, but is virtually absent in countries like Germany and Poland.
According to Abner, the variant isn’t exclusive to Estonia but is found across Eastern Europe. It may have gone undetected in other countries due to the lack of genetic databases like Estonia’s. “That’s one of the strengths of this study. Even though we looked at Estonian genes, the findings provide insight for the entire region,” he said.
For Abner, one of the most interesting aspects of the study was the identification of a distinct group of genes that influence appetite — either maintaining it or helping to signal fullness after eating. “We found unique gene variants in Estonians that are rare elsewhere in the world. These affect how we control hunger and derive satisfaction from food,” he said.
The research also has potential implications for medicine. Popular weight-loss drugs based on semaglutide, such as Ozempic, partly work by activating the POMC gene.
“With semaglutide, people tend to eat less and it’s believed that the POMC gene is involved in that process. If someone has the POMC variant, the drug might not work as expected or might work even better by compensating for a previous deficiency,” Abner said.
If someone has a disrupted version of this gene, the medication could behave differently or not work at all. That’s the next research direction: understanding how genetic background influences drug effectiveness.
Besides POMC, several other novel genes were discovered that could become future drug targets. “Current medications activate one pathway. Perhaps the next generation of drugs can target adjacent pathways even more effectively and safely,” Abner noted.
One surprising discovery was the ADGRL3 gene, previously associated with attention deficit disorder and education level, but not with body weight. “That was unexpected. It seems the same gene that influences focus and learning might also affect eating behavior,” Abner said.
Genes themselves can’t be turned off, so people must work with the genetic cards they’ve been dealt.
“What we can do is use medication to alter how genes function. Awareness of a potential issue helps us find solutions,” Abner said.
In summary, the study suggests that the genetic roots of obesity are often neurological. “If someone says they’re overweight because of their genes, that might be true. But it’s not that the genes make them overweight directly — they change how the brain responds to food,” Abner explained. This helps explain why someone might not resist chocolate, even when they know they should. It’s brain chemistry, not a lack of willpower.
Although genes can explain why some people are more prone to weight gain, that doesn’t mean body weight is unchangeable.
“Genes may guide us, but they don’t determine our destiny,” Abner said. Conscious choices around diet, exercise and sleep remain key. What’s new is a better understanding of why some people find that path more difficult.
“When we understand how the brain and genes work together, we can regulate body weight not through force, but through strategy. It’s hard, of course, but with awareness, it might become easier to stay in control,” he said.
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