Many things influence the chance that someone will develop obesity. That includes genetics. While no single “obesity gene” drives most cases of obesity, researchers are starting to pinpoint which genes carry the strongest risk.
For example, people with certain variants of the SMIM1 gene tend to weigh more and have extra body fat, according to a recent study published in the journal Med. But it’s not a common variant, and many other genes are involved. And genetics usually doesn’t make obesity inevitable; there are often ways to offset the risk.
So says Eleonora Avenatti, MD, DABOM, an obesity and cardio-metabolic specialist at Houston Methodist. She researches the genetics and social determinants of obesity. Here, she answers questions about the link between obesity and genetics.
What genes are linked to obesity?
Avenatti: We know that in some monogenic [single- gene] forms of obesity – the type of severe obesity that’s rare and shows up very early in life – are is the result of a mutation in the leptin (LEP) gene. This gene is responsible for making leptin, a hormone produced in fat tissue that plays an important role in energy metabolism.
But the most common form of obesity, which more than 42% of Americans have, is more complicated than that. It’s not caused by a single gene; rather, more than a hundred of them. Some of the most commonly known are the alpha-ketoglutarate-dependent dioxygenase (FTO) and the melanocortin 4 receptor (MC4R), which is also associated with monogenic obesity.
These genes and many others are linked to obesity but not in a one-to-one, cause-and-effect kind of way. Instead, variants of certain genes interact with our environment, diet, and other social factors to cause obesity.
What do you make of the recent British study identifying SMIM1 as being linked to obesity?
Avenatti: The SMIM1 gene, noted in the Med study, is another example of a gene associated with obesity, although it’s worth noting that there [are] only around 200,000 people with the variant in the entire world. That means that identifying this gene isn’t going to solve the global obesity epidemic.
In this case, this gene likely got passed down because an individual was able to survive famine because they had it and then they reproduced. At some point, variants like this one provided a genetic advantage. But today, our biology and genetic makeup are not necessarily lined up with our current lifestyle.
How much of it is bad eating habits getting passed through generations, and how much of it is our genes?
Avenatti: This is complex and difficult to whittle down. But we do know from studies done on sets of twins separated from their biological parents at birth that their body mass index (BMI) was more similar to their biological parents’ than that of the families with whom they grew up. From this, we can see that there is power in our genetics.
We also know that lifestyle has a very big impact on our BMI. Lifestyle is also somewhat inherited from the families that we grew up around. Another study, published [in July 2024], found that even in those who had a higher genetic risk of obesity, good lifestyle choices could counterbalance that risk.
You’ve said that our BMI doesn’t tell the whole story. What do you mean by that?
Avenatti: It’s important to understand that obesity was only defined as a disease within the last 11 years. We’ve got a long way to go in understanding this very complex and multifactorial condition. The concept of BMI … doesn’t tell the whole story.
While BMI is an important epidemiological measurement that’s helpful in identifying population health, there are ethnic and racial differences in how we’re built and in our metabolisms that are not accounted for in our BMI.
Are there things we can do that influence whether those genes kick into action?
Avenatti: Your genes are not your destiny, but if you’re genetically prone to obesity, you’ll have to work a lot harder not to develop it, similar to if you have a family history of cardiovascular disease.
Having an active lifestyle with some sort of dedicated physical activity is important. As is eating whole unprocessed foods while avoiding fast food, smoking, and moderating alcohol consumption.
Do you anticipate that genetic testing will ever be part of treating obesity?
Avenatti: You can’t gene test for specific genes unless you have the rare monogenic forms of obesity mentioned above. Researchers do use what’s called a polygenic [multi-gene] risk score to look at hundreds of gene variants and provide a prediction of what the risk of obesity could be for a specific person. But polygenic testing is still mostly used in a research setting, not clinically. While we’re not there yet, it is something that could be more widely used in some cases in the future.
