Brain genes associated with increased body mass
15 December 2008
A genetic study of more than 90,000 people has identified six new genetic variants that are associated with increased Body Mass Index (BMI), the most commonly used measure of obesity. Five of the genes are known to be active in the brain, suggesting that many genetic variants implicated in obesity might affect behaviour, rather than the chemical processes of energy or fat metabolism.
Obesity is an increasing problem that results in individual risk to health as well as increasing burdens on healthcare systems. By identifying genetic variants that affect obesity, researchers hope to understand better the mechanisms regulating energy balance, which will guide the development of new therapies and help to develop improved diagnosis.
The study is published in Nature Genetics by the GIANT Consortium and includes authors from more than 60 institutions.
Dr Inês Barroso, a senior author on the study, from the Wellcome Trust Sanger Institute, says:
"It might seem remarkable that it is the brain that is most commonly influenced by genetic variation in obesity, rather than fat tissue or digestive processes. Until 2007, no genetic associations had been found for 'common obesity', but today almost all those we have uncovered are likely to influence brain function."
Increase in weight occurs when calories taken in exceed calories burned, but behind that simple equation lie behavioural processes such as appetite and satiety, as well as the biochemical mechanisms our bodies use to process foods and use stores of energy, such as fat tissue. A part of the brain called the hypothalamus controls many of our basic functions such as body temperature, hunger and fluid balance: it is programmed to maintain the status quo.
Dr Ruth Loos, a leading author from the Medical Research Council Epidemiology Unit, explains:
"Very occasionally, mutations in genes active in the hypothalamus have dramatic consequences for weight gain, such that 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.
Mark McCarthy, Robert Turner Professor of Diabetes at the University of Oxford, a senior author on the paper, says:
"It may seem surprising that we know so little about the biology of such an important medical and social issue. 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 effects of the variants identified in the new study are modest: someone who carries all the risk variants would typically be 1.5-2 kg heavier than an average person. The findings of this study will pave the way for future investigations to uncover more of the elusive variants, perhaps through sequencing of whole genomes, which has become more efficient and cost-effective in the past year or so.
Original research paper: Six new loci associated with body mass index highlight a neuronal influence on body weight regulation is published in Nature Genetics.
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