September 30, 2013
An international team of scientists including a strong Australian contingent has made a key discovery in new research to help find the cause and cure of Multiple Sclerosis (MS).
The team, working under the umbrella of the International Multiple Sclerosis Genetics Consortium (IMSGC), identified 48 previously unknown genetic variants that influence the risk of developing MS.
The discovery nearly doubles the number of known genetic risk factors and thereby provides additional key insights into the biology of this debilitating neurological condition.
The genes implicated by the newly identified associations underline the central role played by the immune system in the development of MS and show substantial overlap with genes known to be involved in other autoimmune diseases such as inflammatory bowel disease, Crohn’s disease and celiac disease.
The study published today in the medical journal, Nature Genetics, is the largest investigation of MS genetics to date.
Relying upon an international team of 193 investigators from 84 research groups in 13 countries, the study was led by the University of Miami Miller School of Medicine and locally across Australia and New Zealand by Associate Professor David Booth, MS Research Australia Senior Research Fellow from the Westmead Millennium Institute, University of Sydney with fellow scientists from the ANZgene Consortium (Australia and New Zealand MS Genetics Consortium).
The research took advantage of ImmunoChip; a custom designed, cutting-edge genotyping technology that targets specific sets of genetic variants linked to one or more autoimmune diseases. IMSGC researchers used the ImmunoChip platform to analyse the DNA from 29,300 individuals with MS and 50,794 unrelated healthy controls, making this the largest genetics study ever performed for MS. DNA from blood samples from 80,000 people both with and without MS were examined, 1800 of which came from Australia and New Zealand.
In addition to identifying 48 new susceptibility variants, the study also confirmed and further refined a similar number of previously identified genetic associations. With these new findings, there are now 110 genetic variants associated with MS. Although each of these variants individually confers only a very small risk of developing multiple sclerosis, collectively they explain approximately 20 percent of the genetic component of the disease.
Associate Professor Booth said the findings represented an important milestone in MS research.
“This publication represents another giant step forward in understanding the genetic contribution to the cause of MS, a step of equal size to that published in Nature in 2011,” he said.
“It shows again the power of global collaboration in pursuit of the cause and cure of the most common chronic neurological disease of young adults. More major discoveries will come from the IMSGC,” Associate Professor Booth added.
Dr. Jacob McCauley from the University of Miami (who led the study on behalf of the IMSGC), commented further on the significance of the work and nature of the collaboration.
“With the release of these new data, our ongoing effort to elucidate the genetic components of this complex disease has taken a major step forward. Describing the genetic underpinnings of any complex disease is a complicated but critical step.
By further refining the genetic landscape of multiple sclerosis and identifying novel genetic associations, we are closer to being able to identify the cellular and molecular processes responsible for MS and therefore the specific biological targets for future drug treatment strategies.
“These results are the culmination of a thoroughly collaborative effort. A study of this size and impact is only possible because of the willingness of so many hard working researchers and thousands of patients to invest their time and energy in a shared goal,” said Dr. McCauley.
The project was funded by more than 40 national agencies and foundations, including support from the Australian National Health and Medical Research Council (Project Grant No.APP633275).
Underpinning the entire research project was the dependency on biobanks, built up over many years from many funding sources around the world.
Dr. Matthew Miles, MS Research Australia’s CEO said, “MS Research Australia is proud to have provided foundation funding and continued support to the ANZgene Consortium.
This work is a huge contribution to our understanding of MS and will underpin intensified efforts to translate these genetic findings into new therapies to reduce the impact of this condition for people with MS world-wide.”
There is currently no cure for MS.