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Researchers Pinpoint Array of Obesity Genes
Date:10/11/2010

By Steven Reinberg
HealthDay Reporter

SUNDAY, Oct. 10 (HealthDay News) -- Scientists have found genes that appear to play a role in the propensity for obesity.

The findings are reported in two new studies published in the Oct. 10 online edition of Nature Genetics.

In one report, researchers say they have identified 18 gene variants linked to obesity and confirmed the involvement of 14 others. In a second report, the same group of researchers say they have identified 13 gene variants that appear to direct fat to the belly or thighs.

"We have made a big leap forward in identifying new gene variations that contribute to the susceptibility to obesity and susceptibility to store fat more on your hips or more on your waist," said researcher Ruth Loos, a group leader in the Genetic Aetiology of Obesity Program in the MRC Epidemiology Unit at the Institute of Metabolic Science, in Cambridge, U.K.

Loos cautioned that these genes cannot be used to predict whether an individual will become obese or not. Right now, they have identified genes linked to obesity, but exactly how these genes work in developing a vulnerability to obesity isn't known, she added.

"But if we know the biology, perhaps we can invent a more effective preventive strategy. Maybe we can identify proteins that we can target with drugs," Loos said. "It's going to take years before these new discoveries will develop into new interventions."

In addition, having these gene variants doesn't mean that an individual is definitely going to be obese. "The prediction is not much better than just flipping a coin," Loos said.

For the first study, Loos and her colleagues looked at data from 46 gene studies that had identified genes linked to body mass index (or BMI, a measurement that takes into account height and weight). Together, these studies included 123,865 people.

In this meta-analysis, which is a review of previously published studies, Loos' group was able to find 18 new genomic regions associated with BMI, and confirm 14 regions that had been identified before.

Loos noted that the more of the gene variants a person has, the greater their susceptibility to obesity. These variants are inherited from both your mother and your father, so you can have as many as 64 variants, she explained.

The average person has about 28 to 32 of these variants; about 2 percent of the population carries more than 38 variants and 2 percent of the population carries less than 21, Loos added.

These genes appear to act in the brain, Loos said. "This suggests that these genes may act through increased food intake -- maybe appetite and reward," she said. "But you still need the environment on top of that to really trigger that susceptibility."

Over the past 30 years, the obesity epidemic has exploded, Loos pointed out. "Our genes haven't changed, our environment has changed," she stated.

However, Loos added, there are several genes whose variants are linked to extreme obesity.

In a second meta-analysis, Loos and colleagues looked at 32 genome-wide studies for genes associated with hip-to-waist ratio, which is a measure of fat distribution. These studies included 77,167 people.

The researchers identified 13 genes associated with hip-to-waist ratio that had not been identified before. Among these genes, seven had a stronger effect on women than men.

These findings show that there are sex-specific genes that regulate fat distribution. Moreover, these genes and the ones in the first study don't overlap, suggesting that different genes regulate BMI and fat distribution.

The differences between where men and women store fat -- men on the waist, women on the thighs -- is likely genetically driven, Loos said.

Obesity expert Dr. David L. Katz, director of the Prevention Research Center at Yale University School of Medicine, said "that there are genes associated with variations in human shape and size is no more surprising than genes associated with variations in eye color, hair color or skin pigment."

Although finding genes associated with obesity is important for understanding the biology of obesity, these new findings have limited application in the current obesity epidemic, Katz said.

"Let us by all means study our genes, and their associations with our various shapes and sizes," he said. "But let's not let it distract us from the fact that our genes have not changed to account for the modern advent of epidemic obesity -- our environments and lifestyles have."

More information

For more information on obesity, visit the U.S. National Library of Medicine.

SOURCES: Ruth Loos, Ph.D., group leader, Genetic Aetiology of Obesity Program, MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, U.K.; David L. Katz, M.D., M.P.H., director, Prevention Research Center, Yale University Medical School, New Haven, Conn.; Oct. 10, 2010, Nature Genetics, online


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