Novel research sheds light on the genetic pathways underlying obesity

A new study has shed light on the genetic factors that underpin obesity. The observations could aid in the development of more personalized methods to assist people in maintaining a healthy weight.

Obesity

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The study is the largest of its kind, focusing on genomics and metabolite levels—the molecules produced by the body when it digests food. It identifies 74 previously unidentified genomic regions that influence how people’s bodies convert food to energy.

The National Institute for Health Research (NIHR) Guy’s and St Thomas’ Biomedical Research Centre supported the research. The study was conducted by researchers from King’s College London’s Department of Twin Research and Genetic Epidemiology and the NIHR BioResource.

The research included 8,809 people representing NIHR BioResource. The BioResource is a database of people who have agreed to be approached about research studies.

The researchers examined blood samples to determine the levels of 722 metabolites. These include a snapshot of a person’s well-being as well as the pathways that control key physiological processes. Nutrition, drugs, and the gut microbiome can all have an impact on metabolite levels. The way a person’s body breaks down food, on the other hand, is known to be greatly influenced by genetics.

The team discovered 202 distinct genomic regions whose variations are linked to the levels of 478 different metabolites after analyzing these alongside whole genome sequencing. These included 74 genomic regions that had not been linked to any metabolites in earlier studies. They confirmed the results in a separate group of 1,768 people.

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.”

Dr Cristina Menni, Study Senior Author, Department of Twin Research and Genetic Epidemiology, King’s College London

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,” Dr Cristina Menni 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.”

Dr Massimo Mangino, Study Lead Author and Senior Bio-Informatician, NHIR Guy’s and St Thomas’ Biomedical Research Centre

Dr 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 UK 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.”

According to the World Health Organization, being overweight or obese claims the lives of over four million people each year.

Source:
Journal reference:

Hysi, P. G., et al. (2022) Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels. Metabolites. doi.org/10.3390/metabo12010061.

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