Professor Jane Worthington and her team at the University's arthritis research campaign (arc) Epidemiology Unit made their findings as part of the largest ever study of the genetics behind common diseases.
The £9M Wellcome Trust Case Control Consortium (WTCCC), which today publishes its results in the journals Nature and Nature Genetics, has given a major boost to the understanding of genetics of seven common diseases, including RA. As well as providing insights into what leads some people to develop the diseases and offering new avenues for treatments, the success of the approach heralds exciting advances in the study of the genetics of disease. It has identified a wealth of genes implicated in coronary heart disease, type 1 and type 2 diabetes, Crohn's disease, bipolar disorder and hypertension, as well as RA. Some of these genes are novel whilst others were known about and have been confirmed by the current study.
Professor Worthington and her team have implicated several genes in the development of RA for the first time. Previously two genes were known to explain 50% of genetically determined susceptibility. Now the team have replicated their results for one of the new genes and are working to validate others.
RA is a chronic inflammatory disease that can affect nearly all joints in the body, particularly the hands and feet. Complications such as lung disease can occur. In addition, patients with RA are more likely to die from cardiovascular disease and some cancers. Some people respond well to treatment, but most suffer a lifetime of disability.
The team will now carry out further work to validate the findings and understand how the variation within key genes influences the development of RA, the course of the disease and the response to treatment.
Dr Anne Barton, a clinician on the team, said: "These are exciting results as RA is a complex, heterogeneous disease with some people suffering inflammation of the hands and feet which comes and goes whilst others develop a progressive form which can quite rapidly result in marked disability. We believe the genes we have found may determine who develops RA or how the severe the disease becomes.
"We also hope that this study may help us to discover why 40-50% of people do not respond to therapy. This therapy is expensive - £8,000 per patient per year for the newest biologic agents that block the inflammatory mediator TNF - and this work could show whether someone would respond well or not in advance, rather than by costly trial and error."
Professor Worthington said: "The WTCCC has been a fantastic example of collaborative effort in the UK. It has taken us to the place we are now, more rapidly and efficiently than if we had tried to undertake this study on our own.
"We had 2,000 DNA samples from patients with RA. By contacting other RA clinicians and researchers in the UK, we now have a further 5,000 samples to take this work forward.
"We are also indebted to the arthritis research campaign (arc), which provided the funding to collect the samples used. This was a huge investment, collecting samples from RA patients over two decades, but it was the sample collection which made it a high quality study."
Professor Peter Donnelly, Chair of the WTCCC, based at the University of Oxford, said: "Many of the most common diseases are very complex, involving both 'nature' and 'nurture', genes interacting with our environment and lifestyles. By identifying the genes underlying these conditions, our study should enable scientists to understand better how disease occurs, which people are most at risk and, in time, to produce more effective, more personalised treatments."
The £9 million WTCCC has been one of the UK's largest and most successful academic collaborations to date, involving 50 leading research groups and over 200 scientists in the field of human genetics from dozens of institutions. For these papers, part of a number of studies due to be published over the next year, the researchers analysed 17,000 DNA samples taken from people in the UK - two thousand patients for each disease and three thousand control samples - to identify common genetic variations for seven major diseases.
Although the human genome is made up of more than three billion sub-units of DNA, called nucleotides (or bases), most of these show little in the way of differences between individuals. The International HapMap Consortium and related efforts demonstrated that a substantial part of the variation in DNA sequence between individuals is due to single-nucleotide polymorphisms (differences), also known as SNPs. There are approximately 8 million common SNPs in European populations. Fortunately, because SNPs that lie close together on chromosomes often tell quite similar stories, researchers in the WTCCC were able to explore this variation through analysing a subset of these SNPs (in fact approximately 500,000).
"Human genetics has a chequered history of irreproducible results, but this landmark collaboration of scientists in Britain has shown conclusively that the new approach of analysing a large subset of genetic variants in large samples of patients and healthy individuals works," says Professor Donnelly. "We are now able to effectively scan most of the common variation in the human genome to look for variants associated with diseases. This approach will undoubtedly herald major advances in how we understand and tackle disease in the future."
The findings have been welcomed by Dr Mark Walport, Director of the Wellcome Trust, the UK's largest medical research charity. The Wellcome Trust not only funded the WTCCC, but also co-funded the Human Genome Project and HapMap.
"Just a few years ago it would have been thought wildly optimistic that it would be possible in the near future to study a thousand genetic variants in each of a thousand people," says Dr Mark Walport, Director of the Wellcome Trust, the UK's largest medical research charity, which funded the study. "What has been achieved in this research is the analysis of half a million genetic variants in each of seventeen thousand individuals, with the discovery of more than ten genes that predispose to common diseases.
"This research shows that it is possible to analyse human variation in health and disease on an enormous scale. It shows the importance of studies such as the UK Biobank, which is seeking half a million volunteers aged between 40 and 69, with the aim of understanding the links between health, the environment and genetic variation. New preventive strategies and new treatments depend on a detailed understanding of the genetic, behavioural and environmental factors that conspire to cause disease."
Jon Keighren | alfa
What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Materials Sciences
06.12.2016 | Medical Engineering
06.12.2016 | Power and Electrical Engineering