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!
Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory
‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications
Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...
Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.
The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
11.12.2017 | Physics and Astronomy
11.12.2017 | Earth Sciences
11.12.2017 | Information Technology