From Our 2010 Archives

New Genes Linked to Obesity, Belly Fat

Research Reveals Genes That Affect Obesity and Where the Extra Fat Goes

By Denise Mann
WebMD Health News

Reviewed by Laura J. Martin, MD

Oct. 11, 2010 -- Your genes may influence how you look in your skinny jeans.

Two studies have identified 18 new genes linked to overall obesity and 13 more that influence whether your weight goes to your belly or to your thighs.

The findings come from the Genetic Investigation of Anthropomeric Traits (GIANT) consortium and appear in Nature Genetics; if validated, they may play a role in how obesity is categorized and treated.

In the first study, researchers conducted an analysis of 46 studies of 123,865 people and identified 18 new genetic regions associated with body mass index (BMI). They also confirmed 14 regions that had been noted before. Some of these genes affect appetite control and others may play a role in metabolism.

The more obesity genes a person had, the greater their risk of being obese, the study showed. Individuals who carried 38 or more BMI-associated genes weighed 15 to 20 pounds more, on average, than those who had fewer than 22, the researchers report. Still, these variants explain only a small fraction of the overall variation in body weight because many other genetic and environmental factors also contribute to obesity risk.

In the second study, researchers analyzed 32 studies of 77,167 people to identify genes associated with hip-to-waist ratio, which is a measure of body fat distribution. Belly fat is a known risk factor for type 2 diabetes and heart disease, while fat stored in the hips and thighs may actually be protective against diabetes and high blood pressure.

This study yielded 13 novel genes, and of these, seven genes had a more pronounced effect among women.

"We know that 50% of our predisposition to weight is genetic and our study is trying to uncover the underpinnings of this," says Elizabeth K. Speliotes, MD, PhD, MPH, an instructor of medicine and gastroenterology at Massachusetts General Hospital and a fellow at the Broad institute in Boston.

The new findings may help explain why blanket recommendations about exercise and eating right just don't work for a lot of people, she says.

"Most of these genes are completely novel, and that tells us that we really didn't understand what we were dealing with in terms of obesity, so it's not surprising that most of our recommendations to control weight don't work," she tells WebMD. "We hope that with further work we can narrow down how these genes work and develop new ways to sub-classify obesity and tailor treatments."

"Genes load the gun, the environment pulls the trigger," says Scott Kahan, MD, co-director of the George Washington University Weight Management Program in Washington, D.C., in an email. "Even as we continue to educate people about obesity, healthy eating, physical activity, etc., ultimately we're not going to get very far until we address the root cause of obesity/weight gain in our population."

"We have a genetic makeup that evolved over millions of years to be effective for thriving as hunter-gatherers (i.e. having minimal food availability, having to search/hunt for food regularly, having regular famines and food scarcity) but we now live in an environment that is very different from what our genes have evolved to do," he says.

"We no longer have to hunt out food, food is incredibly available and dirt cheap, food is now "engineered" to pack an incredible density of calories, famines are now essentially nonexistent in our population, and most of us have to spend our days glued to a chair in order to satisfy job requirements and get our paycheck," he says. "This disconnect is at the root of the obesity epidemic [and] in addition to teaching people about healthy behaviors and such, we need to address the environment and, if possible, our genetic makeup."

SOURCES: Heid, I.M. Nature Genetics, 2010.Speliotes, E.K. Nature Genetics, 2010.Elizabeth K. Speliotes, MD, PhD, MPH, instructor, medicine and gastroenterology, Massachusetts General Hospital; fellow, Broad institute, Boston.Scott Kahan, MD, co-director, George Washington University Weight Management Program, Washington, D.C.

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