Scientists studying the gene maps of thousands of Europeans found three new genetic variations that increase the risk for obesity and said that together with what we already know about genes and obesity the findings could help to develop tools that can predict which young children are at risk of becoming obese.

The study was the work of researchers from Imperial College London, UK, the French National Research Institute CNRS, and other research centres in Europe and Canada, and was published online in Nature Genetics on 18th January.

Ten per cent of children under six in the UK are obese, according to figures from the Department of Health’s National Child Measurement Programme 2007/08.

Co-author Professor Philippe Froguel, from the Department of Genomic Medicine at Imperial College London said:

“When young children become obese, their lives can be affected in a very negative way. Sadly, obese children are often unfairly stigmatised and they can suffer heart and lung problems, painful joints, diabetes and cancer as they grow up.”

The variants discovered in this 10-year study could be responsible for up to 50 per cent of cases of severe obesity, said the researchers.

For the study, they did a genome-wide association study of 1,380 European obese children under six and severely obese adults, and 1,416 age-matched normal weight controls. Most of the obese adults had been obese since childhood or their teenage years.

The researchers found 38 genetic markers with a strong link to a higher than normal body mass index (BMI). They then investigated these in another 14,186 Europeans and found three mutations that are significantly linked to obesity.

The variant that they found to be most strongly linked with childhood obesity and adult morbid obesity is sited near the PTER gene. Nobody knows what this gene does, but the researchers estimated that the variant probably accounts for up to one third of all childhood obesity and one fifth of all severe adult obesity cases.

The second mutation that was strongly linked to childhood and adult obesity was found in the NPC1 gene, which mouse studies have shown to play a role in appetite control (mice without this gene don’t eat much and suffer late-onset weight loss). The researchers estimated that this second variant accounts for about 10 per cent of all childhood obesity and 14 per cent of all cases of severe adult obesity.

The third variant was found near the MAF gene, which controls the making of insulin and glucagon, plus chains of amino acids known as glucagon-like peptides, all of which are important for metabolizing glucose and carbohydrates and in controlling feelings of fullness after eating. The researchers estimated that this variant accounts for about 6 per cent of childhood obesity and 16 per cent of severe adult obesity.

Although the researchers said that more research was needed to see whether these genes are acting independently (it might be the case that they only work together), the joint effect of these new variants could account for up to 50 per cent of all cases of severe adult and childhood obesity.

As Froguel explained, understanding the genetic basis of obesity is the first step, and once we know which genes are responsible:

“We can develop ways to screen children to find out who is most at risk of becoming obese.”

“Hopefully we can then intervene with measures such as behavioural therapy, to make sure a child forms healthy eating habits and does not develop a weight problem,” he added.

The study was sponsored by the Medical Research Council, the Agence Nationale de la Recherche, the Conseil Regional Nord-Pas de Calais / Fonds européen de développement économique et régional, Genome Quebec / Genome Canada and the German Research Council (for the German cohorts).

“Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations.”
David Meyre, Jerome Delplanque, Jean-Claude Chevre, Cecile Lecoeur, Stephane Lobbens et al.
Nature Genetics Published online 18 Jan 2009.
doi: 10.1038/ng.301

Click here for Abstract.

Sources: Journal abstract, Imperial College London.

Written by: Catharine Paddock, PhD