Researchers have identified four genes newly associated with severe childhood obesity. They also found an increased burden of rare structural variations in severely obese children.
The team found that structural variations can delete sections of DNA that help to maintain protein receptors known to be involved in the regulation of weight. These receptors are promising targets for the development of new drugs against obesity.
As one of the major health issues affecting modern societies, obesity has increasingly received public attention. Genes, behavior and environment, all contribute to the development of obesity.
Children with severe obesity are more likely to have a strong genetic contribution. This study has enhanced understanding of how both common and rare variants around specific genes and genetic regions are involved in severe childhood obesity.
"We've known for a long time that changes to our genes can increase our risk of obesity. For example, the gene FTO has been unequivocally associated with BMI, obesity and other obesity-related traits," says Dr Eleanor Wheeler, first author from the Wellcome Trust Sanger Institute. "In our study of severely obese children, we found that variations in or near two of the newly associated genes seem to have a comparable or greater effect on obesity than the FTO gene: PRKCH and RMST."The team found that different genes can be involved in severe childhood obesity compared to obesity in adults.
Some of the children in this study had an increased number of structural variations of their DNA that delete G-protein coupled receptors, important receptors in the regulation of weight. These receptors are key targets for current drug development and may have potential therapeutic implications for obesity.
"Some children will be obese because they have severe mutations, but our research indicates that some may have a combination of severe mutations and milder acting variants that in combination contribute to their obesity," says Professor Sadaf Farooqi, co-lead author from the University of Cambridge. "As we uncover more and more variants and genetic links, we will gain a better basic understanding of obesity, which in turn will open doors to areas of clinically relevant research."
As part of the UK10K project the team are now exploring all the genes of 1000 children with severe obesity in whom a diagnostic mutation has not been found. This work will find new severe mutations that may explain the causes of obesity in other children.
"Our study adds evidence that a range of both rare and common genetic variants are responsible for severe childhood obesity," says Dr Inȇs Barroso, co-lead author from the Wellcome Trust Sanger Institute. "This work brings us a step closer to understanding the biology underlying this severe form of childhood obesity and providing a potential diagnosis to the children and their parents."
Notes to Editors
Publication DetailsEleanor Wheeler, Ni Huang, Elena G Bochukova, Julia M Keogh, Sarah Lindsay, Sumedha Garg, Elana Henning, Hannah Blackburn, Ruth J F Loos, Nick J Wareham, Stephen O'Rahilly, Matthew E Hurles, Inês Barroso & I Sadaf Farooqi (2013) 'Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity.'
This work was supported by the Wellcome Trust at the MRC and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre
Participating CentresWellcome Trust Sanger Institute, Cambridge, UK.
Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
Selected WebsitesThe mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. It admits the very best and brightest students, regardless of background, and offers one of the UK's most generous bursary schemes. The University of Cambridge's reputation for excellence is known internationally and reflects the scholastic achievements of its academics and students, as well as the world-class original research carried out by its staff. Some of the most significant scientific breakthroughs occurred at the University, including the splitting of the atom, invention of the jet engine and the discoveries of stem cells, plate tectonics, pulsars and the structure of DNA. From Isaac Newton to Stephen Hawking, the University has nurtured some of history's greatest minds and has produced more Nobel Prize winners than any other UK institution with over 80 laureates.
Aileen Sheehy | EurekAlert!
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences