A large international consortium study has found at least two gene variants that increase the risk for common childhood obesity. Writing in Nature Genetics on 8 April, the researchers describe how they linked variants near the loci OLFM4 and HOXB5 to this condition, and showed they are also linked with increased body mass index (BMI) in adults.

Lead investigator Dr Struan F.A. Grant, associate director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia in the US, and colleagues write in their background information that while we now know of a number of genes linked to adult obesity, and a handful that are linked to severe childhood obesity, little progress had been made in finding genes behind common childhood obesity.

There is evidence that environmental factors, such as diet and lifestyle have contributed to the increasing rate of childhood obesity, but more recently, studies of twins and families have proposed there may be a genetic contributor to common childhood obesity.

Carrying a gene variant that predisposes a child to obesity does not necessarily mean he or she will develop the condition, but it may explain why among children eating roughly the same diet and having the same lifestyle, there will those who put on more weight.

Grant explained that while their centre at Philadelphia had the world’s largest collection of DNA from children with common obesity, the only way to ensure enough statistical power to carry out a study to find new genes, was to bring together an international body of researchers to combine similar worldwide data sets.

So that is how Grant and the rest of the international Early Growth Genetics (EGG) Consortium, comprising researchers from North America, Australia and Europe, came to carry out the largest ever genome-wide study of childhood obesity, and, as Grant told the press:

“As a consequence, we have definitively identified and characterized a genetic predisposition to common childhood obesity.”

For the meta-analysis, the researchers pooled data from 14 studies covering a total of 5,530 cases of childhood obesity and 8,300 control subjects, all of European ancestry.

In a first pass of the data, they found 8 potential candidate genes linked to early-onset obesity. From these, using statistics to test the strength of the link to childhood obesity, they narrowed the list down to two loci, one near the OLFM4 gene on chromosome 13, the other within the HOXB5 gene on chromosome 17.

The first gene appears to raise the odds of early-onset obesity by 22%, while the other raises it by 14%.

The researchers also tested and showed that both of the loci were linked to severe childhood obesity, and from previous studies, to adult BMI.

They suggest two other variants may also be involved. None of these genes had been linked to obesity before.

Grant said because of their location, we know that three of the genes may influence the biology of the gut, but otherwise we know very little about them.

Grant said the findings open up “new avenues to explore the genetics of common childhood obesity”.

There is still a lot of work to do, he added, but the hope is that the discovery “may ultimately be useful in helping to design future preventive interventions and treatments for children, based on their individual genomes”.

Funds for the study came from the National Institutes of Health in the US, with support from many other European, Australian and North American organizations.

Written by Catharine Paddock PhD