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New Genetic 'Score' Can Predict Risk For Obesity, Study Says

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People at high risk for obesity can struggle to keep weight off despite their diet and exercise habits. (Kim Johnson Flodin/AP)
People at high risk for obesity can struggle to keep weight off despite their diet and exercise habits. (Kim Johnson Flodin/AP)

A new study takes aim at one of the root causes of the obesity epidemic: our genes.

Researchers from Harvard’s Broad Institute have developed a risk “score” derived from genetic testing that can indicate a patient’s likelihood of becoming overweight or obese. They detail their findings in a paper published this morning in the journal Cell.

The study reveals new information about the genetic underpinnings of obesity, a disease that affects almost 40 percent of adults and 20 percent of school-age children in the United States, according to the CDC.

We've had evidence for a long time that obesity is affected by genetics. What this really adds is the ability to distill the risk from the genome into a simple number for each person and look at that number in relation to the rest of the population,” says Dr. Sekar Kathiresan, a cardiologist at Massachusetts General Hospital and one of the authors of the paper.

Obtained from a simple blood test, the score combines the effects of more than 2 million common genetic variants that influence a person’s body mass index (BMI) – a primary measure of obesity – to create a single number for each individual.

That score can then be translated into a percentile that can be compared across a population.

"The numbers follow a beautiful bell curve when you plot them," says Kathiresan. "Like many other traits in the human population, like cholesterol or height, some people are high, some are low and most are in the middle."

The researchers found that adults with a risk score in the top 10th percentile (90th percentile or higher) were more likely to suffer from severe obesity, high blood pressure and heart failure than those in the bottom ten percent.

Using data from the Framingham Heart Study, for example, the authors found that people with scores in the lower 10th percentile developed severe obesity (more than 100 pounds overweight) just 1 percent of the time. For people at higher risk, that number climbed to over 15 percent.

"Some people based on their genome are inherently predisposed to put on weight over their life, and some people are remarkably protected," Kathiresan says.

The authors also found that the obesity risk scores may even predict how much more weight high-risk patients are likely to put on compared to those at lower risk. The 10 percent of people with the highest scores weighed 30 pounds more on average than those with the lowest scores and were 25 times more likely to be obese.

"That's like saying that these folks have inherited a genetic factor that basically makes them put on 30 pounds more than the rest of the population," Kathiresan says.

That genetic factor may manifest itself as early as a person's toddler years, according to the report.

Data from the study's birth cohort revealed only small differences in birth weight between infants with high scores (top 10th percentile) versus those with lower scores (bottom 10th percentile). But the children with high scores started exhibiting elevated weight gain as early as age 3.

Being able to identify children between the ages 3 and 8 who may struggle with obesity could change lives, says Kathiresan.

Imagine if you knew your child was in the 99th percentile from a simple blood test. What might you do differently?” he says.

That question resonates with Sarah Bramblette, whose struggles with weight during childhood left a lasting impression on her adult life.

“There’s a huge amount of weight bias in society that starts from when you’re a kid," she says. "Kids get bullied in school early on because the idea’s out there that you’re just being lazy and eating too much."

Bramblette now sits on the board of directors for the Obesity Action Coalition, an advocacy organization that partners with Tufts Medical Center. She also suffers from a disease called lymphedema, a condition that has caused excess fluids to collect in her tissues.

Her condition may be more the result of one significant genetic mutation, rather than the combination of many smaller genetic factors that researchers focused on in this study. But Bramblette says the stigma surrounding a person's weight persists no matter the cause.

Her hope is that more scientific discovery can further the conversation of obesity as a disease rather than a "willpower" problem.

There are people out there who have excess weight who want healthier habits and just cannot seem to lose the weight because there's something in our biology that is working against us," she says. "When you look at other diseases, like heart disease and cancer, there's not just one thing that causes them. And no one blames you when you come out of remission."

That stigma isn't likely to go away overnight even with the new findings, says Dr. Fatima Cody Stanford, an obesity medicine physician at Massachusetts General Hospital Weight Center.

"I don't think it will ever be eradicated," she says. "It's just like we haven't completely eradicated racism, bias against people of lower socioeconomic statuses or people with disabilities. These things are deeply ingrained in us."

Furthermore, while Stanford believes this study is an important step in obesity research, she wonders how applicable the results will be for minority patients.

According to the CDC's 2015-2016 statistics, Hispanic and non-Hispanic black adults experienced a disproportionately high prevalence of obesity (47 and 46.8 percent prevalence in adults, respectively) compared to non-Hispanic white (37.9 percent) and Asian Americans (12.7 percent).

The authors of this study acknowledge that their findings - based on data from primarily European countries - are likely to provide more accurate predictions for weight gain in white patients than patients from other races and ethnic groups. While Stanford says some people of African descent, for example, are likely included in the study, there probably aren't enough for a truly representative sample.

"I do think that we have to take this with a grain of salt because we can't immediately apply this to populations of color," she says. "It's important for us to continue to push the envelope to recognize minorities that are disproportionately affected but often understudied."

The ultimate goal of the research, says Kathiresan, is to eventually help prevent obesity in as many patients as possible. For though the study's findings highlight the connections of genetics to weight, he maintains that "DNA is not destiny."

"Those who have high scores are going to have a much harder time keeping the weight off, but they're not fated to have the problem," he says. "Individuals who are susceptible can help themselves with better lifestyle choices."

Related:

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Khari Thompson Producer, Radio Boston
Khari Thompson is a producer for Radio Boston.

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