Scientists have discovered rare gene differences that could raise the risk of obesity by as much as six times. Led by Medical Research Council (MRC) researchers, the study identified genetic variants in two genes that have some of the largest impacts on obesity risk discovered to date. Experts suggest the discovery of rare variants in the BSN and APBA1 genes are some of the first obesity-related genes identified for which the increased risk is not observed until adulthood. Professor Giles Yeo, study author based at the MRC Metabolic Diseases Unit, said: “We have identified two genes with variants that have the most profound impact on obesity risk at a population level we’ve ever seen, but perhaps more importantly, that the variation in Bassoon 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.” The researchers used data from the
UK Biobank and other information to perform whole exome sequencing – a type of genetic sequencing used to understand what may be causing symptoms or a disease – of body mass index (BMI) in more than 500,000 people. They found that genetic variants in the gene BSN, also known as Bassoon, can raise the risk of obesity by up to six times. It was also associated with an increased risk of non-alcoholic fatty liver disease and of type 2 diabetes. The Bassoon gene variants were found to affect one in 6,500 adults, suggesting they could affect about 10,000 people in the UK. Professor John Perry, study author 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.” Obesity is a significant risk factor for other serious diseases, including heart disease and type 2 diabetes. However, the genetic reasons why some people are more prone to weight gain are not completely understood. Unlike the obesity genes identified in previous studies, variants in BSN and APBA1 are not associated with childhood obesity. This led the researchers to believe they may have uncovered a new biological mechanism for obesity. Based on published research and their laboratory studies, the scientists suggest age-related neurodegeneration could be affecting appetite control. For the new study, the researchers worked closely with AstraZeneca to replicate their findings in existing groups using genetic data from people from
Pakistan and
Mexico. This is important as the researchers can now apply their findings beyond people of European ancestry. The findings are published in Nature Genetics.