Scientists Reveal Genetic Link That Leads to Weight Gain and Obesity

Scientists have uncovered new genetic variants that might lead to bulging waistlines among individuals.

The variants map close to a gene called MC4R. MC4R protein plays a key role in regulation of appetite and energy expenditure and mutations in these genes lead to weight gain.

"By working together with many international groups we have been able to assemble a sample collection which was large enough to allow this finding to be made," Nature quoted Dr Ruth Loos, leading author from the Medical Research Council Epidemiology Unit, as saying.

"Several groups had shown that rare, highly disruptive variants in the MC4R gene were responsible for very severe, genetic forms of obesity: this collaboration has uncovered more common variants that affect more people," Loos added.

The team from the Cambridge GEM consortium (Genetics of Energy Metabolism) and Oxford University and a collaboration between 77 institutions from the UK, USA, France, Germany, Italy, Finland and Sweden analysed 77,000 adults and discovered two copies of genetic variants that resulted in an average increase in weight of about 1.5 kg.

Previous studies demonstrated the a role for the FTO gene, which showed that people carrying two copies of an FTO variant are about 2-3 kg heavier than those who have no copies of the variant.

The recently discovered variants act along with the variants of the FTO gene and individuals carrying variants in both genes were found to be, on average, 3.8 kg heavier.

"This is a great example of how cooperation can bring about new findings that can be missed when researchers work in isolation," said Dr Ines Barroso, Investigator at the Wellcome Trust Sanger Institute and one of the senior authors on the study.

"The precise role in obesity of genetic variants in FTO and near MC4R remains to be discovered, but we can now begin to understand the biological consequences of these variants. This is where this research will make a difference," Barroso added.

The new variants lie some distance from the MC4R gene. The team suspect that the sequence variant changes activity of the MC4R gene, perhaps by disrupting DNA regions required for normal activity of MC4R.

"Through this new and powerful genetic approach we are increasingly finding that the genes known to play a role in severe - but rare - diseases are also implicated in much more common disease," said Professor Mark McCarthy, Robert Turner Professor of Diabetes at the University of Oxford, UK.

The study also found that the effects were almost double in children between the age of four and seven. This more dramatic effect in young children reflects the more extreme consequences seen with rare variants of MC4R that severely disrupt its activity, suggesting that the novel variants do indeed exert their effect through action on MC4R.

The study appears in journal Nature Genetics.

Source-ANI
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