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Brain background to body mass
Date:12/14/2008

people carrying these mutations are severely obese. Such mutations might be considered exceptional.

"However, we suggest that the picture for common obesity is very similar: many or most genes associated with increased BMI are active in the brain."

Studies in twins suggest that genetics can account for 40-70% of the variation in BMI. Yet only one of the genes that were previously discovered had been thought to be linked to increased BMI or obesity in humans. The six new candidate genes provide a rich pool of resources to understand some of the processes in the brain that drive increased BMI and common obesity.

They also highlight the role of different types of mutation: intriguingly, one of the variants does not seem to mark a single-base change in the human genome, but rather the loss of a region of DNA of around 45,000 bases. The authors suggest that this lack of genome sequence near a gene called NEGR1might knock out genomic sequences that regulate activity of NEGR1. Such a variant has not been previously detected in studies of common obesity.

"It may seem surprising that we know so little about the biology of such an important medical and social issue," says Mark McCarthy, Robert Turner Professor of Diabetes at the University of Oxford, a senior author on the paper. "We can use genetics to open the door on some of the processes that contribute to individual differences in the predisposition to obesity. We are finding that common diseases have complex causes, and it is only by understanding the biology that we can start to make rational attempts to treat and prevent conditions such as this.

"Studies such as this are uncovering more and more genetic changes that are involved in more and more diseases. This is a remarkable time for human genetics."

The authors point out that perhaps dozens of similar variants remain to be discovered. The effects of the variants identified in the new study are modest: someone wh
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Contact: Don Powell
don@sanger.ac.uk
44-012-234-96928
Wellcome Trust Sanger Institute
Source:Eurekalert

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