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New insights into the genetics of body shape

11 October 2010

Whether you’re apple- or pear-shaped is partly down to your genes, according to new research published today. Two major studies published in ‘Nature Genetics’ have revealed new insights into the biological processes that are involved in determining body fat distribution and obesity.

We already know that where we store fat in our bodies has important implications for our health. Carrying more fat around the waist - the classic 'apple' shape - is associated with increased risk of type 2 diabetes and heart disease. On the other hand, being pear-shaped, with more fat stored around the thighs and bum, has been suggested in some research to offer some protection against diabetes and high blood pressure.

Our waist-to-hip ratio is a good measure of this difference in body fat distribution, and is known - like predisposition to obesity - to be determined to some extent by the genes we inherit.

There are also clear differences in body shape between men and women, but the body processes that determine these differences are not well understood.

In the first study, an international team of scientists, led by researchers at Oxford University and the Medical Research Council (MRC) Epidemiology Unit in Cambridge, completed a large genome-wide search for DNA variations that could be connected to waist-to-hip ratios. They identified 13 new gene regions linked to body fat distribution, and confirmed the one previously known genetic link. The study shows that these genetic variations affect waist-to-hip ratio, separate from any effect on overall obesity.

Seven of the identified genetic variations have much stronger effects in women than in men, suggesting differences in fat distribution between the sexes.

Although the gene regions identified explain only around 1 per cent of the variation in waist-to-hip ratios in the population, they do point toward specific biological mechanisms that are involved in regulating where the body stores fat. These gene regions are involved in regulating cholesterol, triglyceride levels, insulin and insulin resistance.

"By finding genes that have an important role in influencing whether we are apple-shaped or pear-shaped, and the ways in which that differs between men and women, we hope to home in on the crucial underlying biological processes," says Dr Cecilia Lindgren, senior researcher on the study at the Wellcome Trust Centre for Human Genetics at Oxford University.

"Understanding biology through finding genes is just a first step in a long journey towards treatment, but it is a vital one. As efforts to tackle obesity through changes in lifestyle or by different treatment options have proved extremely challenging, the potential to alter patterns of fat distribution may offer an alternative for future drug discovery."

In a second study, researchers looked for genes connected to body mass index (BMI), a measure commonly used to classify adults as overweight (BMI of 25-29.9) or obese (BMI of 30 or greater). They found 18 new genetic regions that are associated with increased susceptibility to obesity, more than doubling the DNA variations we know about that are reliably linked to BMIs up to 32.

Some of the new findings indicate the involvement of genes active in the brain that influence our appetite and also genes involved in the control of insulin levels and metabolism.

The study also showed that people who inherit many of the BMI-increasing DNA variants from their parents weigh 7-9 kg more than those who inherit few of these variants. This difference in weight is solely due to the fact that the people differ genetically. Despite the large difference between the most susceptible and the least susceptible, the 32 confirmed genetic associations still only explain 1.45 per cent of the variation seen in people's BMIs, suggesting there are many more genetic associations still to be found.

"We have conducted the largest ever genome-wide association study so far, and by including almost 250 000 individuals we have been able to identify 18 new genetic regions associated with obesity," says Dr Ruth Loos, senior researcher on the study at the MRC Epidemiology Unit in Cambridge.

"These two studies are the beginning of new insights into the biology of obesity and body shape, which in turn may lead to more targeted approaches to obesity prevention and the potential to the develop new drugs. We should not forget that, while the genetic contribution to obesity is substantial, a large part of obesity susceptibility remains down to our lifestyle."

The studies were carried out by the Genetic Investigation of Anthropometric Traits (GIANT) consortium, an international collaboration of more than 400 scientists from 280 research institutions with support from many funding agencies worldwide.

Image: Man sitting on a park bench. Credit: Tobyotter on flickr

Reference

Head I et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet 2010.

Speliotes E et al. Association analyses of 249 796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010.

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