A genetic test may one day predict a child’s risk of obesity in adulthood, paving the way for early interventions.
Certain genetic variants can affect how a person’s body stores fat or make them more prone to overeating. Genetic variation can also predict how well a person will respond to different weight loss drugs.
In a study published Monday in the journal Nature Medicine, more than 600 researchers from around the world worked together to compile genetic data from more than 5 million people — the largest and most diverse genetic dataset to date. They also used genetic data from 23andMe.
From the dataset, the researchers were able to create what’s known as a polygenic risk score, which takes into account which genetic variants a person has that have been linked to a higher BMI in adulthood.
The score, the researchers said, could be used to predict a person’s risk of obesity as an adult — before they even turn 5.
“Childhood is the best time to intervene,” said study co-author Ruth Loos, a professor at the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research. (Research conducted at the center is not influenced by drugmaker Novo Nordisk, though some of the study authors had ties to pharmaceutical companies that make weight loss drugs.)
The findings come as obesity is rising around the world. Rates of obesity in adults have more than doubled globally since 1990, and adolescent rates have quadrupled, according to the World Health Organization. About 16% of adults worldwide have obesity and the situation is worse in the United States, where more than 40% of adults have obesity, Centers for Disease Control and Prevention statistics show.
Twice as effective
The new test is not the first that predicts a person’s risk of obesity, but Loos and her team showed it was about twice as effective as the method doctors currently use to assess their patients. That polygenetic score can account for about 8.5% of a person’s risk for having a high BMI as an adult. The new score increased that to about 17.6%, at least in people with European ancestry.
“That’s a pretty powerful risk indicator for obesity, but it still leaves open a lot that is unknown,” said Dr. Roy Kim, a pediatric endocrinologist at Cleveland Clinic Children’s who was not involved with the research.
Based on this score, more than 80% of a person’s risk for obesity can be explained by other factors, such as where they live, what kinds of foods they have access to, and how much they exercise.
The test was not nearly as effective in predicting obesity risk in non-Europeans. It explained about 16% of the risk for having a high BMI in East Asian Americans, but just 2.2% in rural Ugandans.
About 70% of people whose data was included in the study were of predominantly European ancestry. About 14% were Hispanic and typically had a mix of ancestries. About 8% were of predominantly East Asian descent and just under 5% were of predominantly African ancestry. These samples were predominantly from African American people, who largely had mixed ancestry. Just 1.5% were of predominantly South Asian ancestry.
Loos said the new score is a big step forward, but that it’s still a prototype. The next step is to collect more — and more diverse — data on people with African ancestry in particular to improve how well the score works for everyone, not just white people.
She said the score could offer one indicator — what high blood pressure is to heart disease, for example — that could help predict a person’s risk of developing obesity.
“Obesity is not only about genetics, so genetics alone can never accurately predict obesity,” Loos said. “For the general obesity that we see all over the world, we need other factors such as lifestyle that need to be part of the predictions.” Genetics play a bigger role in severe obesity, meaning a BMI of more than 40, she added.
Still, identifying a person’s genetic risk early on in childhood and intervening early with lifestyle coaching could make a big difference, she said. Research has shown that about 55% of children with obesity go on to have obesity in adolescence, and that about 80% of those individuals will have obesity in adulthood.
“Behavioral things are really important,” Kim said. “Their environment, their access to healthy food, exercise opportunities, even their knowledge about healthy foods all affect a person’s obesity risk.”
How important are genetics, really?
Although studies in identical twins have found that genetics can account for as much as 80% of the reason a person has obesity, lifestyle factors still play a huge role, Kim said.
“Even with the same genetic makeup, people can have different body types,” he said. “From a very young age in my practice, we educate patients about the importance of eating protein-rich foods, a lot of fruits and vegetables and not too many refined carbs.”
Dr. Juliana Simonetti, co-director of the Comprehensive Weight Management Program at the University of Utah, has been using genetic testing in her adult patients for about five years. She said understanding a person’s genes can help doctors better treat weight gain.
“Obesity is not homogeneous. We have different kinds and different presentations,” said Simonetti, who wasn’t involved with the new study.
Simonetti uses a person’s genes to determine if a patient struggles with satiety, or feeling full.
“They eat but do not feel full,” Simonetti said, adding that this is a disorder caused by genetic mutations affecting certain pathways in the body. People who have these mutations “tend to have higher weight,” she said.
But such mutations do not tell the whole genetic story of obesity, Simonetti said. The genes that a person inherits from either parent, even if they are not mutations, also determine how a person’s body stores weight or uses energy. Both can play a big role in obesity risk.
Genetic testing is also starting to be able to determine how well certain weight loss drugs will work for a person, Simonetti said, but she added this is just the beginning.
“We are talking about three out of 80 mutations that we can treat,” she said. “We are getting better, and the more data we have, I’m hopeful that we are going to do a better job in being more precise in understanding treatment responses.”
