Scientists Find New Genetic Variants for Obesity

Researchers believe they have discovered a new biological mechanism for obesity, pointing to rare variants on two genes that dramatically increase the risk of carrying excess weight.

Research published in the journal Nature Genetics on Thursday points to variants that raise the chance of being obese by as much as six times. Unlike other known variants that affect weight gain in children, these only appear to play a role in adults.

Unraveling obesity’s mechanisms could help scientists develop new drugs, or tailor existing ones, for a condition that now affects one in eight people. For the first time, patients can now take highly effective medicines to shed unwanted weight. The revolution, led by drugmakers Novo Nordisk A/S and Eli Lilly & Co., carved open a market that could surpass $100 billion globally by 2030.  

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Using data from over 500,000 people, scientists from the Medical Research Council at the University of Cambridge found variants in two genes called BSN and APBA1 that increased the risk of obesity in adults. 

The variants in BSN, also known as Bassoon, were associated with an increased risk of diabetes and fatty liver disease. The Bassoon variants affect about 1 in 6,500 adults, the researchers said.  

The hypothesis is that as people who have these gene variants get older, neurons in their brain start to degenerate, removing “some of the key circuits within the brain controlling food intake and therefore you end up with obesity,” said Giles Yeo, one of the authors of the study and a professor at the MRC Metabolic Diseases Unit.

The Bassoon variant may one day help drugmakers develop preventive medicines, according to Yeo. The question would be, “can we actually slow down the process, prevent the process from happening to begin with, so that then we prevent more people from ending up with obesity, particularly in adulthood.” 

The researchers used the UK Biobank database and worked with AstraZeneca Plc to check that their findings applied beyond people of European ancestry, using data from Pakistan and Mexico.

Astra is one of the latest drugmakers to join the obesity race, having clinched a deal last year to buy an experimental pill that’s still in early-stage tests.