MS and the Human Genome: A HealthCentral Explainer

CRegal Editor
  • A recent study from Oxford University has identified a genetic variant linked to multiple sclerosis (MS) that will limit the efficacy of a certain class of drugs that works for other patients.  The gene TNFRSF1A has previously been associated with the risk of developing MS; only now has the variation been identified as being the agent that actually blocks the power of anti-TNF medications. 


    Though this discovery will not lead to a cure for MS and will only directly impact a small number of people, it does open the door to the use of genetics to study MS.  According to Lars Fugger, a professor in the Nuffield Department of Clinical Neurosciences, "The hope has been that analyses of the whole human genome would lead to findings that are clinically relevant."   

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    What hope does the study of the human genome provide for treating MS?

    The Human Genome Project was a 13-year project coordinated by the U.S. Department of Energy and the National Institutes of Health, in collaboration with the Wellcome Trust (U.K.) as well as Japan, Germany, China and others.  The goals of the project were to identify all of the 20,000 to 25,000 genes in human DNA, determine the sequences of the 3 billion chemical base pairs that make up DNA and deliver this information to the private sector for future study, while taking into consideration the ethical issues associated with the project.  The Human Genome Project was completed in 2003.


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    Three studies published in 2007 offered the first significant breakthroughs in the identification of the cause of MS.  The studies, published in Nature Genetics and the New England Journal of Medicine, were able to locate the first three genetic variations associated with the condition.  


    In 2009, researchers from the Australia and New Zealand Multiple Sclerosis Genetics Consortium were able to identify new locations on the chromosome that could lead to increased susceptibility to MS. 


    In a 2010 study published in Nature, scientists analyzed the genetic make-ups of identical twins, where one twin had MS and one did not.  The study found that in 30 percent of cases where one twin has MS, so does the other.  This study found a change in the human leukocyte antigen region of chromosome 6 as being one genetic variation that could lead to MS.  However, the researchers also noted that there were significant environmental factors, including Vitamin D deficiency and sun exposure, that could also contribute to the development of MS. 


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    In 2011, a team of researchers from the University of Cambridge summed up the findings from the 10 total genome-wide association studies, which had previously attempted to identify the cause of MS.  Ultimately, there were 16 loci – the aforementioned location of a DNA sequence on a chromosome – associated with MS. 


    In the most significant breakthrough to date, 29 new genetic variations associated with MS were identified in August 2011.  This was a product of the largest MS genetics project ever, studying nearly 10,000 MS patients.  Interestingly, one-third of the 29 variations are also associated with other autoimmune diseases, leading one to question if there is a significant link. 


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    However, as Dr. J.R. Oksenberg and S.E. Baranzini wrote in a 2010 paper, "our knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed."  They added, "The ensuing challenge will be to design effective functional studies that convincingly link genetic variation to the underlying pathophysiology of MS" (Oksenberg et al , 2010).


    Though these cumulative findings have not been able to fully identify a definitive cause for MS or led directly to its cure, this will open the doors to new approaches towards potential therapies.  It should change the way scientists can formulate new medications and clinical trials can be performed with a greater knowledge of the testing base. 



    Australia and New Zealand Multiple Sclerosis Genetics Consortium.  (July 2009).  "Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20."  Nature Genetics, 41(7): 824-828. 


    Baranzini, S.E., et al., (29 April 2010).  "Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis." Nature, 464(29):1351-1356.


    BBC News.  (9 July 2012).  "Gene flaw 'explanis why drugs failed to treat MS.'" BBC News: Health.  Retrieved from


    Human Genome Project.  (25 July 2011).  "Human Genome Project Information."  Genomics.Energy.Gov.  Retrieved from


    The International Multiple Sclerosis Genetics Consortium and The Wellcome Trust Case Control Consortium.  (11 August 2011).  "Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis."  Nature, 476 (7359): 214-219.


    Kemppinen, A., Sawcer, S., Compston, A. (March 2011).  "Genome-wide association studies in multiple sclerosis: lessons and future prospects."  Briefings in Functional Genomics, 10(2): 61-70. 


    News Medical.  (30 June 2007).  "Genome detectives discover culprits in multiple sclerosis."  News Medical.  Retrieved from


    Oksenberg, J.R., Baranzini, S.E. (August 2010).  "Multiple sclerosis genetics – is the glass half full, or half empty?"  Nature Reviews Neurology, 6(8): 429-437. 


Published On: August 01, 2012