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This Score Can Tell You Your Genetic Risk for Obesity. Is It Worth Knowing?

There can be a 30-pound weight difference between people with low and high genetic risk. But genes aren’t everything.

ByKatherine J. WuNOVA NextNOVA Next
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Researchers now have the tools to score an individual's genetic risk for obesity. Genes aren't everything—but they might influence a person's weight as early as age three. Image Credit: Vasyl Dolmatov, iStock

Someday, in the not-so-distant future, new parents might have the option of having their children’s fates forecast at birth. These prophecies, which might reveal everything from an individual’s height to their risk of developing a certain disease, will arise not through readings of tea leaves or tarot cards, but of DNA.

Although there are many ethical and scientific hurdles to overcome, the toolkit of genetic prediction continues to grow. The latest addition? A score that tabulates an individual’s inborn risk for obesity, published today in the journal Cell.

The metric, which compiles information from more than two million spots in the genome that affect a person’s weight, isn’t a perfect predictor of physique. But adults that score in the top 10 percent are, on average, almost 29 pounds heavier than those in the bottom 10 percent—and it appears that genetically driven differences in weight can materialize as early as age three.

“This work is, overall, an important contribution,” says Charles Rotimi, a human geneticist at the National Institutes of Health who was not involved in the study. “It takes advantage of all the genetic resources we’re getting out of [studies of human genetics]...and takes into account a lot of the variation we’ve found with obesity.”

Regardless of its performance, however, Rotimi and other experts advise caution in interpreting the results. Weight is certainly affected by genes, but “a genetic score can never fully predict obesity,” says Ruth Loos, a human geneticist at the Icahn School of Medicine at Mt. Sinai who was not involved in the study. “Lifestyle and environmental factors remain equally, if not more, important.”

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It’s long been clear that lifestyle changes like a healthy diet and regular exercise can help stave off weight gain. But the genetic side of this equation has always been far murkier. Like most traits, weight isn’t controlled by the flip of a single molecular switch. Dozens, possibly hundreds, of genes can affect a person’s risk of becoming obese—and scientists are nowhere close to finding and characterizing them all.

The score detailed in the study, however, has a workaround. In recent years, researchers have found over 2.1 million genetic alterations—equivalent to single-letter typos—that are more prevalent in obese individuals.

Even without knowing what the underlying genes actually do, scientists can still tally up the tweaks in any given individual. The result integrates information scattered across the genome into a single, interpretable number, “almost like a cholesterol score,” says study author Sekar Kathiresan, a cardiologist and human geneticist at Massachusetts General Hospital.

When Kathiresan and his team put their score to the test in a population of 300,000 adults, it accurately stratified groups of individuals by weight, body mass index (BMI), and prevalence of obesity. For instance, when arrayed by score, people in the top 10 percent were 25 times more likely to be severely obese, with a BMI of at least 40 kilograms per square meter, than those in the bottom 10 percent.

“How striking these differences are...is what got us so excited,” Kathiresan says. “The tremendous differences between the two ends of the spectrum are remarkable.”

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Environmental factors and genetics both play into weight. But while a lot is known about the lifestyle choices that can influence obesity, the genetic side is far murkier. Image Credit: Rostislav_Sedlacek, iStock

The technology isn’t ready for use in the clinic. But the researchers are hoping to create a low-cost test—maybe around $50 per patient—that could use an easy-to-take sample like blood to scour the genome for obesity-related variants.

Making this kind of information widely available could be an important step toward reducing cultural stigma around obesity, which can both cause undue emotional hardship and dissuade people from seeking effective treatment. “Obesity is viewed as a problem of willpower,” Kathiresan says. “We blame the patient. What this [score] says is, ‘There’s a big biological underpinning that’s not necessarily within their control.’”

Such stigma is frustrating, given that obesity isn’t always disease-related, Rotimi says. “Not all of these people have diseases like diabetes,” he says. “There are people who are very heavy, but are doing fine.”

But those individuals are the exception, rather than the norm. High-scoring adults in the study were also more likely to suffer from several heart-related conditions—including coronary artery disease, diabetes, heart failure, and stroke—and had higher rates of overall mortality.

Of course, most adults don’t need a genetic test to tell them whether or not they’re overweight, Kathiresan says. Genetic tests remain far more costly than stepping on a scale. These types of scores could still be explanatory, however—by offering someone perspective on why they’ve struggled to shed excess weight, for instance.

And there’s still a large contingent of people who might be able to use these scores to guide weight-based interventions—in themselves, or perhaps even their kids, says study author Amit Khera, a cardiologist and geneticist at Massachusetts General Hospital. The scores didn’t perform quite as well in children, but differences in body mass were discernible in individuals as young as three years old. “There’s no question that the impact takes effect very early in life,” Khera says. “A major goal is to use this info to empower people to offset inherited risk.”

Before any of that can happen, though, it’s important to acknowledge how much of obesity can’t be captured by this score, Loos says. In its current iteration, the test makes predictions that are often incorrect: About 40 percent of the highest-scoring adults were obese—but that leaves 60 percent that weren’t (and the accuracy drops further in younger populations). This could tread into tricky territory, especially if parents end up making lifestyle decisions on behalf of their children before the kids themselves can have a say, Rotimi says.

In the end, there are limits to what even the most rigorous genetic scans can tell us. A perfect, diversity-conscious genetic test would still capture only a fraction of what’s feeding the obesity epidemic, Loos says.

Altogether, these considerations could limit such a score’s utility in the clinic. “If we introduce a test into health care that is not predictive enough to be useful, then we are basically making health care more inefficient,” says Cecile Janssens, an epidemiologist and genomics researcher at Emory University who was not involved in the study. Even if the test is free, any interventions will require substantial public health investment, putting the onus on researchers to make these scores as accurate as possible, she says.

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Human genetics research is accelerating at an unprecedented pace. But most studies are still done in populations of European ancestry. Image Credit: undefined, iStock

How this sort of information is doled out also needs to be carefully handled. The nature of the research reflects good intentions, Rotimi says, but “if we don’t carefully weigh the overall implications of these recommendations, we may indeed do more harm than good.”

While some individuals might be able to use a high score as motivation to be extra-conscious about their weight, others might feel like their fates are sealed by these genetic report cards, Loos says. Researchers have conducted similar risk assessments in the past with mixed results. In one study, disclosure actually backfired: People informed that they had a high genetic risk for obesity increased their fat intake in the months after receiving the news. The uptick was temporary, but this kind of behavior, wherein people effectively resign themselves to what they see as genetic destiny, is definitely cause for concern, Loos says.

The converse could cause problems as well, Rotimi says. Just as there are individuals who might carry a higher risk for obesity, so, too, exist those who are a little more protected from it. Getting an ultra-low score might make some people think they can eat and do whatever they want, he says. And no one is immune to the repercussions of persistently unhealthy behavior.

There’s another big caveat. One of the largest limitations of the study is the fact that it was conducted exclusively with data from individuals of European ancestry. Based on previous research, these scores will apply to everyone, but will work best in those of European descent, Khera says. Leveling the playing field will require expanding research to include other groups.

With these issues in mind, the ultimate message is about striking a balance between nature and nurture. “This speaks to the fact that the endpoint of obesity is the result of genetics as well as lifestyle,” Kathiresan says.

And for many, that could actually be a silver lining: Genes are powerful—but we still have a lot of control over our own bodies. “People who are susceptible may have to work harder to keep weight off,” Kathiresan says. “But it’s important to know that they can, with great success.”

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