Genetic Insights into Pathways Behind Obesity Uncovered

Genomenon said today it has partnered with Rhythm Pharmaceuticals to create a database of genetic mutations associated with obesity as documented in published studies. Rhythm plans to use the data to better understand rare genetic disorders of obesity. [Visual Mozart/Getty Images]

A genome-wide association study led by King’s College London has uncovered new information about genetic pathways underlying obesity, which could help develop more personalized ways to help people maintain a healthy weight.

“Metabolites are small products of metabolism that provide a snapshot of the well being of an organism and the mechanisms that control key physiological processes involved in health and disease,” the researchers wrote. “Here we report the results of a genome-wide association study of 722 circulating metabolite levels in 8,809 subjects of European origin, providing both breadth and depth.”

The findings are published in the journal Metabolites. From analyzing these alongside whole genome sequencing, the team observed 202 unique genomic regions whose variations are associated with the levels of 478 different metabolites. These included 74 genomic regions not associated with any metabolites in previous works.

Senior author Cristina Menni, from the department of twin research and genetic epidemiology, King’s College London said: “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.”

Their findings may have potential for identifying novel targets and developing new therapeutic strategies for obesity.

“Some of the metabolites we looked at are linked to body mass index and could give us an insight into obesity in some individuals,” continued Menni. “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.”

Massimo Mangino, senior bio-informatician from the NHIR Guy’s and St. Thomas’ Biomedical Research Centre and lead author of the study, added: “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. By teasing out the complex relationships between different genes, we have a huge opportunity to turn the tide against this condition.”

Pirro Hysi, from the department of twin research and genetic epidemiology, concluded: “This study is the largest scale study of its kind of metabolite levels to date and its results enhance our knowledge of genetic mechanisms controlling human metabolism. The NIHR BioResource is a unique U.K. resource made possible by the amazing collaboration between doctors and researchers in the NHS. It’s because of collaborations like this that large scale studies like ours are possible.”

The new findings pave the way for the development for more personalized strategies to help people maintain a healthy weight.

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