Scientists have identified six new genes that are associated with increased Body Mass Index (BMI), the most commonly used measure of obesity.
Five of the genes identified are known to be active in the brain, which suggests that many genetic variants implicated in obesity might affect behaviour, rather than the chemical processes of energy or fat metabolism.
The study involving more than 90,000 people was conducted by the GIANT Consortium, included authors from more than 60 institutions.
"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," Nature Genetics quoted Dr. Ines Barroso, a senior author on the study, from the Wellcome Trust Sanger Institute, as saying.
"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," Dr. Barroso said.
The authors have revealed that the new genetic mutations were observed in a part of the brain called the hypothalamus, which controls basic functions like body temperature, hunger and fluid balance.
"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," said Dr. Ruth Loos, a leading author from the Medical Research Council Epidemiology Unit.
"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," the researcher added.
The authors hope the identification of the six new candidate genes will help improve scientists' understanding of some of the processes in the brain that drive increased BMI and common obesity, and guide the development of new therapies and improved diagnosis.
"We can use genetics to open the door on some of the processes that contribute to individual differences in the predisposition to obesity," says Mark McCarthy, Robert Turner Professor of Diabetes at the University of Oxford, a senior author on the paper.
According to authors, 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.
They say that this finding will open the door for the identification of more of the elusive variants, as they believe that perhaps dozens of similar variants remain to be discovered.
The authors say that future research could harness the power of longitudinal cohort studies, which track the health of many subjects through time, thereby providing the tools to map gene-environment interactions.
"As we uncover more variants, we will gain a better basic understanding of obesity, which in turn will open doors to previously unimagined areas of clinically relevant research. We hope that these advances will guide the development of more effective treatments and interventions," said Joel Hirschhorn, Associate Professor of Genetics at Children's Hospital/Harvard Medical School and at the Broad Institute.