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Genes behind obesity mapped in large-scale study

An international research team has identified seven new gene loci linked to obesity. Researchers were also able to show that the genetic mechanisms that cause extreme obesity are similar to those that cause milder forms of overweight and obesity.

A total of more than 260,000 people were included in the study of the links between genes and obesity, which will be published in the latest issue of Nature Genetics. The aim of the study was to identify new genes that increase the risk of obesity, but also to compare genetic factors that cause extreme obesity with those that are linked to rest of the BMI range.

"We know from experience that genetic factors are important for the emergence of both milder and more extreme forms of obesity, but how much overlap there is between genes that are involved in extreme obesity and normal or slightly elevated BMI has not been examined systematically previously," says Erik Ingelsson, Professor at the Department of Medical Sciences and Science for Life Laboratory, Uppsala University, who coordinated the study.

The researchers studied gene variants, or positions in the genetic code that differ between individuals. Many million such commonly occurring inherited differences are scattered throughout the genome. In the recently published study, researchers identified loci (regions of the genome) that are linked to obesity through examining the relationship between different body measurements and 2.8 million gene variants in 168,267 participants.

They then carried out a targeted follow-up of the 273 gene variants with the strongest link to various body measurements in another 109,703 people. Through this extensive gene mapping they were able to confirm the majority of the gene loci which were already linked to various body measurements, as well as identifying four new gene loci linked to height, and seven loci linked to overweight and obesity. They could also demonstrate a great overlap of genetic structure and distribution of gene variants between extreme forms of obesity and milder forms.

"This knowledge is important because it increases the biological understanding of the origins of extreme obesity as well as milder forms of obesity. Our results suggest that extremely obese individuals have a greater number of gene variants that increase the risk of obesity, rather than completely different genes being involved. In the long term, our findings may lead to new ways of preventing and treating obesity, which is one of the greatest global public health problems of our age," says Erik Ingelsson.

The study is also important because it indicates that conclusions from genetic studies of the most extreme cases of a certain characteristic, such as extreme obesity, may be generalized to the rest of the population. This is important knowledge for the design of future studies.

The present study was carried out within the framework of the research consortium GIANT (Genetic Investigation of ANthropometrical Traits) which has gathered over one hundred partial studies and more than 300 co-authors. The study was coordinated by Erik Ingelsson, who is one of the leaders of the consortium, together with researchers from several leading research institutes in the United Kingdom and the United States.

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