The secret to whether or not you’re at risk for obesity could be partially locked into your genes at birth.
Now, a team of researchers from the Broad Institute of MIT and Harvard, Massachusetts General Hospital, and Harvard Medical School has developed a genome screening-based “polygenic score” to help quantify that future obesity risk.
The scientists analyzed 2.1 million sections of the human genome related to body weight (“polygenic” literally means “many genes”) and ran this through a recently developed computer algorithm.
They first validated and then tested it against the weight data from 119,000 individuals and 288,000 individuals, respectively.
The researchers found that people who scored in the top 10 percent of markers for genetic obesity risk were 25 times as likely to be severely obese as those who scored in the lowest 10 percent.
That amounted to a difference of almost 30 pounds on average.
People in this high-risk group also had a 28 percent higher risk for coronary artery disease, a 72 percent higher risk for diabetes, a 38 percent higher risk for high blood pressure, and a 34 percent increased risk for heart failure.
So, are we ready to find out our kids’ obesity risk through a blood test?
Not quite, the study authors say.
“A high polygenic score doesn’t necessarily mean someone is fated to become obese,” Dr. Sekar Kathiresan, a study co-author and director of the cardiovascular disease initiative at the Broad Institute and a professor of medicine at Harvard Medical School, said in a press release.
“DNA is not destiny. We know that a healthy lifestyle can offset a genetic predisposition, although those with a high genetic risk likely have to work much harder to maintain a normal weight,” he said.
In other words, this polygenic scoring clarifies and improves upon the idea that obesity risk is partially genetic and not merely a matter of willpower.
It could also provide opportunities for early intervention.
“Given that the weight trajectories of individuals… start to diverge in early childhood, such interventions may have maximal effect when employed early in life,” the researchers write in their study.
Some researchers are more critical of the current limits of genetic testing and its usefulness to the general public.
“Obesity is partly genetic, partly due to lifestyle. Heritability is around 50 percent,” Ruth Loos, PhD, director of the Genetics of Obesity and Related Metabolic Traits Program at Mount Sinai Hospital in New York, told Healthline.
“But the other 50 percent is because people have different lifestyles, different diets, different physical activity levels, and so on,” she added. “So, if you have a genetic score — and even if it was a perfect genetic score — you still only capture half of people’s genetic susceptibility. You still cannot accurately predict future obesity because you don’t capture the lifestyle part.”
With regards to this study, she says, the score is far from perfect or predictive.
She points out that among the top 10 percent of highest polygenic scores in the study, 58 of 371 developed severe obesity.
That still left 313 who didn’t.
Similarly, there were 166 people in the middle 80 percent who did develop obesity, despite not having the highest number of risk factors.
“So you can wonder, is it ethical to scare people when they’re actually not developing obesity?” she said.
The researchers themselves note this polygenic score system is an improvement on other models that account for far fewer genetic variants in their paper, but they said it’s far from complete.
While they envision a future where this polygenic scoring is useful for assessing the risk of a number of diseases, they call for careful study of precisely those outliers “who maintain normal weight despite an unfavorable score or develop severe obesity despite a favorable score.”
Instead, they hope this research furthers “a clear understanding of the genetic predisposition to obesity [that] may help to de-stigmatize obesity among patients, their healthcare providers, and the general public.”
“We are in the early days of identifying how we can best inform and empower patients to overcome health risks in their genetic background,” Dr. Amit V. Khera, the lead study author, clinician, and member of the research faculty in the Massachusetts General Hospital Center for Genomic Medicine, said in the press release. “We are incredibly excited about the potential to improve health outcomes.”
For now, better predictive measures of future obesity may already exist.
Loos says her own calculations found that family history is still a better predictor of future obesity than genetic testing — albeit also an imperfect one.
That’s because family history tells a story both about a person’s genetics as well as their environment and culture. That is, both sides of the coin.
“Family history captures genes but also lifestyle, family environment, and how you raise your children, which has a big effect on future risk,” she said. “Also the socioeconomic environment. Individuals with less money [have] less money to spend on health food.”
The benefit of early prediction is that it might be more empowering than finding out your markers of genetic risk as an adult.
“Obesity is very different from cancer,” she said. “It’s sort of looming in the future. You sort of feel you’re in control (with other diseases) because it’s not there yet. With obesity, by your 20s or 30s, you’re typically in it or not in it.”
Whether it’s a genetic score or a family workup, the question remains: What can people do to stave off obesity if they fall into a high-risk group?
There’s the individual side: Try to eat healthy, exercise, and maintain appropriate daily caloric intake.
Then there’s the structural side, which might require a more comprehensive approach.
That, Loos says, is more difficult to figure out.
“We need societal measures,” she said. “We need a food industry that is genuine about trying to make people eat healthy foods, about offering healthy goods at the right price.”