Study finds yet another obesity gene

Obesity is a risk factor for many diseases.
It's been clear to scientists for a while that heredity plays a role in obesity. But figuring out which genes are involved -- and how -- has proved as complicated as human metabolism itself.
Geneticists have estimated that a person inherits 30 percent to 70 percent of a tendency to be fat or thin (or body mass index) from his or her parents.
At least 70 mutations or variants of 10 genes have been implicated in obesity thus far, but just how common the mutations are in people or groups of people is not always clear.
An estimated 65 percent of Americans are overweight, and 30 percent are considered obese. Obesity is a risk factor for a variety of diseases, including diabetes, stroke and high blood pressure.
A new study -- which used a pioneering statistical technique to test more than 86,000 DNA sequence variations -- has identified yet another gene variant that's linked to BMI, an obesity index based on the ratio of weight to height.
And after studying the DNA samples from five study groups, the researchers calculated that the obesity-predisposing genotype is present in about 10 percent of populations around the world.
What's suggested
Such widespread distribution suggests that the variant has been common in humans for a long time. And, like other gene mutations related to fat storage and eating habits, it probably gave a competitive advantage to early humans who lived with the uncertain food supplies associated with hunting and gathering, only becoming a liability with the abundant food supplies of modern times.
The study, published today in the journal Science, started with blood samples taken from nearly 700 participants in the landmark Framingham Heart Study, which has tracked heart disease through three generations of residents of the Massachusetts town since 1948.
Normally, a search for one gene variant most tied to obesity out of a field of tens of thousands would use a two-step process that first selected a smaller group of candidates, then a second round of screening.
But using a technique developed by the Harvard School of Public Health that estimated the extent that genetics can explain variations in a specific trait, the researchers found a single candidate.
The variant lies near an insulin-induced gene (INSIG2) that's known to produce a protein that controls the burn rate of fatty acid and cholesterol.
"Although these variants are likely to carry low relative risk, their impact on health is substantial because of their [widespread] prevalence in the population," wrote the team led by Alan Herbert, a professor at Boston University School of Medicine.
With the new obesity culprit in hand, the researchers joined with scientists at other institutions to determine if the variant could also be linked to an increased risk of obesity in other groups.
Those studies confirmed the same association in four of five independent groups, including those of Western European ancestry, blacks and children, and which included both families and unrelated subjects. The analysis also confirmed that people had to have inherited two copies of the mutation to face the increased risk of obesity.

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