Rare gene differences can cause sixfold increase in risk of obesity

Scientists have discovered rare gene differences that can cause a sixfold increase in the risk of ­obesity.

Scientists have discovered rare gene differences that can cause a sixfold increase in the risk of ­obesity. Picture: iStock

Scientists have discovered rare gene differences that can cause a sixfold increase in the risk of ­obesity.

The study, which used data from the UK Biobank, identified variants in two genes that have some of the biggest impacts on obesity discovered to date.

The variants in the BSN and APBA1 genes are some of the first obesity-related genes found where the risk does not increase until adulthood.

Giles Yeo, a co-author of the study, based at the Metabolic ­Diseases Unit of the Medical ­Research Council, said: “We have identified two genes with variants that have the most profound impact on obesity risk … we’ve ever seen, but perhaps more importantly, that the variation in Bassoon [the BSN gene] is linked to adult-onset and not childhood obesity.

“Thus these findings give us a new appreciation of the relationship between genetics, neuro­development and obesity.”

Led by the MRC researchers, scientists used data from the UK Biobank to perform whole-­genome sequencing of body mass index in more than 500,000 people. The research, published in the journal Nature Genetics, found that variants in the Bassoon gene can increase the risk of obesity by up to six times. The variant was also associated with an increased risk of non-alcoholic fatty liver disease and type 2 diabetes.

These variants affected one in 6500 people.

Obesity is a big risk factor for other serious diseases, such as heart disease and type 2 diabetes, though the genetic reasons some people are more prone to gain weight are not wholly understood.

John Perry, a co-author of the study and an MRC investigator at the University of Cambridge, said: “These findings represent another example of the power of large-scale human population genetic studies to enhance our understanding of the biological basis of disease.

“The genetic variants we identify in BSN confer some of the largest effects on obesity, type 2 diabetes and fatty liver disease ­observed to date, and highlight a new biological mechanism regulating appetite control.”

Dr Giles Yeo. Picture: SBS TV

Researcher Slave Petrovski.

Unlike the genes found in previous research to be linked to obesity, the BSN and APBA1 variants are not associated with childhood obesity. This led the researchers to believe they had found a new biological mechanism for obesity.

This relation to adult obesity, together with previous research and their laboratory studies, led the scientists to suggest age-­related neuro-degeneration could be affecting appetite control.

The team of scientists worked with AstraZeneca to replicate their existing findings on the gene using data from people in Pakistan and Mexico.

Slave Petrovski, vice-president of the Centre for Genomics Research at AstraZeneca, said of the collaboration: “Rigorous large-scale studies such as this are ­accelerating the pace at which we uncover new insights into human disease biology. By collaborating across academia and industry, leveraging global datasets for validation and embedding a genomic approach to medicine more ­widely, we will continue to improve our understanding of disease – for the benefit of patients.”

THE TIMES