Up to 10,000 people in Britain could have rare genetic quirks that make them up to six times more likely to become obese, a study suggests.
Obesity affects around a quarter of all adults in Britain and increases the risk of conditions such as type 2 diabetes, stroke and coronary heart disease.
But the genetic reasons why some people are more prone to weight gain are poorly understood.
Now researchers have discovered genetic variants in two genes that have one of the biggest impacts on obesity risk to date.
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The proportion of Britons who are overweight or obese has grown slowly over time, reaching two-thirds in 2021, the latest available data shows. No data has been recorded for 2020, the year of the Covid pandemic
The team, based at the University of Cambridge, analyzed the genes of more than 500,000 individuals in Britain to look for rare variants responsible for obesity.
They discovered that genetic variants in the BSN gene, also known as Bassoon, can increase the risk of obesity as much as six times.
The quirk was also linked to an increased risk of non-alcoholic fatty liver disease and type 2 diabetes.
The bassoon gene variants were found to affect one in 6,500 adults – so could affect around 10,000 people in Britain.
A rare variant of a gene called APBA1 was also found to increase the risk of obesity.
The researchers said these are some of the first identified obesity-related genes for which the increased risk does not affect children, but only adults.
They suggest that the Bassoon and APBA1 genes play a role in the transmission of signals between brain cells, which could influence appetite control as a person ages.
Study author Professor John Perry said: ‘These findings represent another example of the power of large-scale genetic studies in human populations to advance our understanding of the biological basis of disease.
‘The genetic variants we identify in BSN cause some of the largest effects on obesity, type 2 diabetes and fatty liver disease observed to date and highlight a novel biological mechanism regulating appetite control.’
Nearly 4.3 million people were living with diabetes in 2021/22, according to the latest figures for Britain. And another 850,000 people have diabetes and are completely unaware of it, which is worrying because untreated type 2 diabetes can lead to complications including heart disease and stroke.
The researchers said understanding the neural biology of obesity could provide more potential drug targets to treat the condition in the future.
Professor Giles Yeo, who also worked on the study, said: ‘We have identified two genes with variants that have the most profound impact on obesity risk at a population level that we have ever seen, but perhaps more importantly that the variation in bassoon is related to obesity in adults and not obesity in children.
‘These findings therefore give us a new appreciation for the relationship between genetics, neurological development and obesity.’
As part of the study, the researchers collaborated with biopharmaceutical company AstraZeneca to test their findings in cohorts of patients from other countries.
This is important, they said, because it shows they can apply their findings to other people of European descent.
Dr. Slavé Petrovski, vice president of the Center for Genomics Research at AstraZeneca, said: ‘Rigorous large-scale studies like this accelerate the pace at which we discover new insights into the biology of human disease.
‘By working together across academia and industry, using global datasets for validation and more broadly embedding a genomic approach to medicine, we will continue to improve our understanding of disease – for the benefit of patients.’