Another replenishment
74 new genome regions associated with obesity have been discovered
Mikhail Orlov, Naked Science
A new large-scale study performed in the UK on 8809 subjects revealed 74 new genome regions that are associated with obesity. This work has become an important contribution to the study of the mechanisms of obesity and human metabolism in general, and its result can become the basis for new methods of personalized therapy.
"Obesity and related diseases are one of the most important sources of health problems. However, its biological mechanisms have not been sufficiently studied," says Dr. Massimo Mangino, head of the team of authors of a new article in the journal Metabolites (Hysi et al., Metabolome Genome—Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels). He works as a senior bioinformatics researcher in one of the divisions of the National Institute of Medical Research of Great Britain (NIHR Biomedical Research Centre).
The study was the largest of its kind. A total of 8,809 people took part in it — all of them are included in a large bank of volunteers for biomedical research BioResources. The scientists analyzed the content of 722 metabolites (metabolic products) in their blood plasma, thereby obtaining a detailed assessment of everyone's health status. It is known that the level of metabolites is influenced by nutrition, medication intake, as well as the intestinal microbiome. Genetic factors, such as mutations and traits inherited from parents, are also of great importance.
The sample includes people with both normal and overweight — men and women of different ages. The authors adjusted for the gender 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 a Genome-Wide Association Study (GWAS) — now such studies have become an important tool for geneticists and doctors to link specific mutations with their effect on health.
Statistically significant associations with obesity were found for many genetic markers at once. Such markers are not randomly scattered throughout the genome: they are distributed across 197 unique clusters located at a considerable distance from each other. For 74 sections of the genome, the connection with metabolism was revealed for the first time.
The analysis confirmed that the concentration of most metabolites really strongly depends 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 (an anomaly in the synthesis of bile acids) and the UMPS gene affected by hereditary orotic aciduria (deficiency of the enzyme uridine monophosphate synthase).
One of the authors of the study, Dr. Christina Menni from King's College London, is optimistic: "These results can have many practical applications. Human metabolism is the basis of various aspects of his health, as well as the development of diseases. Our research helps to understand this better. Some of the metabolites considered are related to the body mass index and help to understand how obesity develops in each individual. So far, these are preliminary results and we hope that in the future they will become the basis for new methods of weight correction that take into account genetic individuality."
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