Obesity-linked 74 new genome regions discovered

(ORDO NEWS) — A new large-scale study carried out in the UK on 8809 subjects immediately identified 74 new genome regions that are associated with obesity.

This work became an important contribution to the study of the mechanisms of development of obesity and, in general, human metabolism, and its result may become the basis for new methods of personalized therapy.

“Obesity and related diseases are one of the biggest sources of health problems. However, its biological mechanisms are not well understood, ”says Dr. Massimo Mangino, team leader for a new article in the journal Metabolites . He is a senior bioinformatics researcher in a division of the NIHR Biomedical Research Center.

The study has become the largest of its kind. A total of 8809 people took part in it – all of them included in the large bank of volunteers for biomedical research BioResources.

Scientists analyzed the content of 722 metabolites (metabolic products) in their blood plasma, thereby obtaining a detailed assessment of the health status of each. Nutrition, medication, and the gut microbiome are known to affect metabolite levels. Genetic factors are also of great importance – mutations and traits inherited from parents.

The sample includes people with both normal and overweight – men and women of different ages. The authors corrected for the sex and age of the subjects, as well as their body mass index, in order to avoid errors associated with these factors.

The researchers examined over 10 million genetic markers, that is, individual small sections of the genome. They performed the Genome-Wide Association Study (GWAS), which has now become an important tool for geneticists and physicians to link specific mutations to their health effects.

Statistically significant associations with obesity were found at once for many genetic markers. Such markers are not randomly scattered throughout the genome: they are distributed over 197 unique clusters located at a considerable distance from each other. For 74 regions of the genome, the relationship with metabolism was revealed for the first time.

The analysis confirmed that the concentration of most metabolites is indeed highly dependent on genetic factors.

It is noteworthy that some of these sites are associated with already known rare hereditary metabolic disorders. For example, the region of the CYP27A1 gene , mutations in which cause cerebrotendinous xanthomatosis (abnormal synthesis of bile acids) and the UMPS gene , affected by hereditary orotic aciduria (deficiency of the enzyme uridine monophosphate synthase).

One of the study’s authors, Dr. Christina Menney of King’s College London, is optimistic: “These results have many practical applications. Human metabolism is the basis for a wide variety of aspects of his health, as well as the development of diseases.

Our research helps to better understand this. Some of the metabolites discussed are associated with body mass index and help to understand how obesity develops in a particular person. So far, these are preliminary results and we hope that in the future they will form the basis for new methods of weight correction, taking into account the genetic personality.”


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