Genetic pathways underlying obesity discovered

Analysing genetic pathways linked to metabolism has moved researchers one step closer to understanding the genetics of obesity.

Researchers from King's College London (KCL) and the UK government agency the National Institute for Health Research's BioResource collaborated to correlate genomic regions with metabolite levels. Metabolites are molecules produced as a by-product of digestion. The genome-wide association study, identified 74 regions of the genome that influence metabolism, which had not been associated with any metabolites in previous research.

'Some of the metabolites we looked at are linked to BMI and could give us an insight into obesity in some individuals. It is very early research, but in the future, these findings could help to develop approaches to maintaining a healthy weight which take into account a person's genetic profile,' said senior author Dr Cristina Menni from KCL.

For each of the 8809 participants, who were of European origin, scientists measured the blood levels of 722 metabolites, which were compared alongside whole genome sequencing. The researchers unearthed 202 unique genomic regions whose variations were found to relate to 478 different metabolites, including 74 genetic regions previously unknown to be related to metabolism. The scientists further confirmed their findings in an independent group of 1768 participants who were also of European origin.

Metabolites with significant genetic links with BMI can provide useful insights into metabolic dysregulation and obesity. Dr Massimo Mangino, joint lead author from KCL, said: 'Obesity is one of the most common conditions, and yet there's still so much we need to understand about its biological mechanisms. Our latest findings may help to unravel some of them. Genetic studies hold real promise in helping us find new treatments for obesity.'

Publishing their findings in the journal Metabolites, the authors attributed the new discoveries to the 'breadth and depth' of their investigation and even though the research is at an early stage, the researchers believe that these results could have far-reaching applications across healthcare: 'These results could have many practical implications. Human metabolism underlies a lot of different areas of human health and disease. Our findings could help understand certain diseases.' concluded Dr Menni.

The findings also shed new light on the genetic causes of rare diseases such as cerebrotendinous xanthomatosis, where the body's ability to break down fat is impeded, leading to progressive neurological dysfunction. Other findings involved methotrexate, an anti-cancer therapy. Genetic regions were discovered that correspond to sensitivity to methotrexate and may be related to how effective the drug is to a patient.