Genetic testing reveals new genes and variants linked to MS disease progression

MS study finds genetic variant associated with faster disease progression

Cambridge University Hospitals NHS Foundation Trust has announced findings from a study involving more than 22,000 people with MS, which identifies “the first genetic variant associated with faster disease progression”.

Through the study, two large MS research consortia – The International Multiple Sclerosis Genetics Consortium and The MultipleMS Consortium – worked together to allow MS researchers from around the world to “pool the resources needed to begin to identify the genetic factors influencing MS outcomes”. The international collaboration involved more than 70 institutions from around the world, led by researchers from University of California, San Francisco and the University of Cambridge.

The researchers combined data from over 12,000 people with MS to complete a genome-wide association study, using statistics to link genetic variants to particular traits. The “traits of interest” in this case were related to MS severity, “including the years it took for each individual to advance from diagnosis to a certain level of disability”.

More than 7 million genetic variants were sifted through before scientists identified one said to be “associated with faster disease progression”. The variant in question “sits between two genes with no prior connection to MS, called DYSF and ZNF638”. The former is involved in repairing damaged cells, and the latter helps to control viral infections. According to the researchers, “the variant’s proximity to these genes suggests that they may be involved in disease progression”.

Dr Adil Harroud, lead author of the study and former postdoctoral researcher in the Baranzini Lab, states: “These genes are normally active within the brain and spinal cord, rather than the immune system. Our findings suggest that resilience and repair in the nervous system determine the course of MS progression and that we should focus on these parts of human biology for better therapies.”

The use of statistical methods known as ‘Mendelian randomisation’ also helped the team to discover that “years of education and parental age reduced the severity of MS, while smoking worsened it.”

Professor Stephen Sawcer, Cambridge co-senior author, commented: “Understanding how the variant exerts its effects on MS severity will hopefully pave the way to a new generation of treatments that are able to prevent disease progression. Although it seems obvious that your brain’s resilience to injury would determine the severity of a disease like MS, this new study has pointed us towards the key processes that underlie this resilience.”

Looking to the future, CUH notes that further work is necessary to to determine exactly how genetic variant affects the two genes in question, and the wider nervous system.