Is DNA your destiny when it comes to gaining weight?

Why is it that some people seem to gain weight by just looking at a piece of cake, while others can pack away large meals without packing on the pounds?

It doesn’t seem fair, but the fact is leanness comes naturally to some. And now a comprehensive new study on the genetics of obesity reveals why this might be so. The researchers identified rare gene variants that protect some lucky carriers from gaining weight.

The researchers examined mutations within genes that were associated with a lower or higher body mass index (BMI), the most reliable measure of obesity. They found 16 genes tied to BMI, some of which are expressed in the hypothalamus, the area of the brain that regulates hunger and metabolism. Those who carried variants that inactivate one of these genes—GPR75—weighed an average of 5.3 kilograms less and had half the odds of being obese compared to those with working copies of the gene. The variants that inactivate this gene are thought to be quite rare with only one in 3,000 people carrying it.

One of the impacts of this finding is that the discovery of these rare variants could lead to new medication treatments for people struggling with obesity.

And that’s good news because obesity is an epidemic. In the U.S. more than 40 percent of the population is considered obese (in Canada it’s closer to 30 percent).

At least 2.8 million people die every year from being overweight or clinically obese. Obesity increases the risk of developing type 2 diabetes, heart disease, some cancers, and even severe COVID-19. 

So is DNA destiny when it comes to gaining weight? There are many factors that determine a person’s chances of being obese, including diet, exercise and ill health. A healthy diet and regular exercise can offset a genetic predisposition but these people may have to work harder to maintain a normal weight.

Approximately 10 percent of a person’s obesity risk may be determined by their DNA, according to the authors of a 2019 study published in the journal Cell, which examined data from 2.1 million genetic variants to identify adults at risk of severe obesity.

The researchers found that a genetic predisposition to obesity begins to appear in early childhood and is often clearly evident by early adulthood — suggesting an opportunity for early intervention.

“We’ve known for a long time that some people are born with DNA predisposing them to obesity,” says one of the study authors, Dr. Amit V. Khera, a clinician and researcher at the Massachusetts General Hospital Center for Genomic Medicine. “Now, we can quantify those differences in a meaningful way, and potentially explore new routes for achieving better health.”