New study highlights limitations of current genetic testing for obesity

A new study has identified key gaps in current genetic testing approaches for obesity, suggesting that more comprehensive analysis is needed to identify individuals with a genetic predisposition to the condition. The findings highlight the value of whole-exome sequencing over existing obesity gene panels and call for a rethink of current testing criteria.

Obesity remains a major public health concern, with both environmental and genetic factors contributing to its development. While the heritability of body mass index (BMI) is estimated at 40–80 per cent, distinguishing between the genetic subtypes of obesity remains a diagnostic challenge. Obesity can be broadly categorised as polygenic or monogenic, although recent research suggests these groups may overlap more than previously thought.

Polygenic obesity arises from the cumulative effect of numerous common genetic variants, each contributing modestly to overall obesity risk. In contrast, monogenic obesity results from a single gene variant that significantly increases susceptibility, often leading to severe obesity from an early age.

In this study, researchers reviewed the genetic test results of 521 individuals living with obesity. Of these, 84.7 per cent underwent whole-exome sequencing, while 15.3 per cent were tested using a large gene panel. Monogenic obesity was diagnosed in 5.8 per cent of cases and a further 7.1 per cent carried a potentially obesogenic variant, bringing the total to 12.9 per cent.

The study found higher diagnostic yields in children (6.3 per cent) and individuals living with syndromic obesity (7.0 per cent). Interestingly, the diagnostic yield was lower among patients living with severe obesity, challenging assumptions that genetic testing should be limited to those with extreme cases.

Crucially, 40 per cent of patients identified as living with monogenic obesity had variants in genes not currently included in standard obesity panels. This highlights the inadequacy of existing tests and underlines the superiority of whole-exome sequencing in uncovering clinically relevant genetic variants.

The authors conclude that obesity gene panels need to be updated to include overlooked syndromic genes and that broader access to whole-exome sequencing could improve diagnosis and personalised care for individuals living with obesity of genetic origin.