Scientists have identified 29 new genetic variants linked to multiple sclerosis, providing key insights into the biology of a very debilitating neurological disease. Many of the genes ¬implicated in the study are relevant to the immune system, shedding light onto the immunological pathways that underlie the development of multiple sclerosis.
The research, involving an international team of investigators led by the Universities of Cambridge and Oxford and funded by the Wellcome Trust, is published today, 11 August, in the journal Nature. This is the largest MS genetics study ever undertaken and includes contributions from almost 250 researchers as members of the International Multiple Sclerosis Genetics Consortium and the Wellcome Trust Case Control Consortium.
Multiple sclerosis is one of the most common neurological conditions among young adults, affecting around 2.5 million individuals worldwide. The disease results from damage to nerve fibres and their protective insulation, the myelin sheath, in the brain and spinal cord. The affected pathways - responsible in health for everyday activities such as seeing, walking, feeling, thinking and controlling the bowel and bladder - are prevented from 'firing' properly and eventually are destroyed. The findings announced today focus attention on the pivotal role of the immune system in causing the damage and help to explain the nature of the immune attack on the brain and spinal cord.
In this multi-population study, researchers studied the DNA from 9,772 individuals with multiple sclerosis and 17,376 unrelated healthy controls. They were able to confirm 23 previously known genetic associations and identified a further 29 new genetic variants (and an additional five that are strongly suspected) conferring susceptibility to the disease.
A large number of the genes implicated by these findings play pivotal roles in the workings of the immune system, specifically in the function of T-cells (one type of white blood cell responsible for mounting an immune response against foreign substances in the body but also involved in autoimmunity) as well as the activation of 'interleukins' (chemicals that ensure interactions between different types of immune cells). Interestingly, one third of the genes identified in this research have previously been implicated in playing a role in other autoimmune diseases (such as Crohn's Disease and Type 1 diabetes) indicating that, perhaps as expected, the same general processes occur in more than one type of autoimmune disease.
Previous research has suggested a link between Vitamin D deficiency and an increased risk of multiple sclerosis. Along with the many genes which play a direct role in the immune system, the researchers identified two involved in the metabolism of Vitamin D, providing additional insight into a possible link between genetic and environmental risk factors.
Alastair Compston from the University of Cambridge who, on behalf of the International Multiple Sclerosis Genetics Consortium, led the study jointly with Peter Donnelly from the Wellcome Trust Centre for Human Genetics, University of Oxford, said: "Identifying the basis for genetic susceptibility to any medical condition provides reliable insights into the disease mechanisms. Our research settles a longstanding debate on what happens first in the complex sequence of events that leads to disability in multiple sclerosis. It is now clear that multiple sclerosis is primarily an immunological disease. This has important implications for future treatment strategies."
Peter Donnelly, who leads the Wellcome Trust Case Control Consortium, added: "Our findings highlight the value of large genetic studies in uncovering key biological mechanisms underlying common human diseases. This would simply not have been possible without a large international network of collaborators, and the participation of many thousands of patients suffering from this debilitating disease."
For additional information please contact:
Genevieve Maul, Office of Communications, University of Cambridge
Tel: direct, +44 (0) 1223 765542, +44 (0) 1223 332300
Mob: +44 (0) 7774 017464
Jonathan Wood, Press Officer, University of Oxford
Tel: +44 (0)1865 280530
Notes to editors:
1. The paper 'Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis' will be published in the 11 August edition of Nature.
2. The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk
3. For more information about multiple sclerosis, please contact:
In the UK: The Multiple Sclerosis Society in the UK (http://www.
Helpline number 0808 800 8000 (9am-9pm weekdays)
In the USA: National MS Society's web site (www.nationalMSsociety.org)