• Posted April 4, 2024

Rare Genes Can Raise Odds for Obesity 6-Fold

Two newly discovered genetic variations can have a powerful effect on a person's risk for obesity, a new report says.

Variants in the gene BSN, also known as Bassoon, can increase risk of obesity as much as sixfold, researchers report April 4 in the journal Nature Genetics.

These variants affect about 1 in every 6,500 adults, researchers said.

Variants of the APBA1 gene also are associated with increased obesity risk, results show.

“We have identified two genes with variants that have the most profound impact on obesity risk at a population level we've ever seen,” said researcher Giles Yeo, a professor with the Medical Research Council's Metabolic Diseases Unit at Cambridge University.

Previous genetic variants associated with obesity have been linked to the brain pathways normally associated with appetite regulation, known as the leptin-melanocortin pathway, researchers said.

Interestingly, neither the BSN nor the APBA1 gene are known to be involved in that brain pathway, researchers said.

Instead, prior studies have found that these genes play a role in the transmission of signals between brain cells -- suggesting that age-related brain declines might affect appetite control.

Further, neither gene is associated with childhood obesity risk, researchers said.

For the study, researchers used data from the UK Biobank genetic research project to perform genetic sequencing of body mass index in more than a half-million people.

They found that the BSN gene variants also had other health effects, such as increasing risk of type 2 diabetes and non-alcoholic fatty liver 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,” researcher John Perry, a professor at Cambridge, said in a university news release.

More information

The Harvard T.H. Chan School of Public Health has more on obesity and genetics.

SOURCE: University of Cambridge, news release, April 4, 2024