MS Functional Genetics

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease with genetic and environmental components to susceptibility. Pathologically, there are perivenular infiltrates of CD4+ T cells in the central nervous system (CNS) white matter and meninges with demyelinating lesions and loss of axons in both white and gray matter. Genome-wide association studies (GWAS) have led to the identification and validation of several MS susceptibility loci which are likely to affect many different aspects of immune responses that contribute to the onset of MS.

A proportion of MS patients experience disease activity despite treatment. The early identification of the most effective drug for a given individual is critical to impact long-term outcome and to move toward a personalized treatment approach. Recently, we reported the discovery of a genetic variant that is associated with a patient’s likelihood of responding to interferon-beta, one of the medications used in treating multiple sclerosis (MS). Published in the Annals of Neurology on May 14, 2015, our study also presents evidence that the affected gene, SLC9A9, may have a broader role in regulating the development and activity of certain immune cells that play important roles in inflammatory diseases like MS.

Our studies will potentially provide a mechanism of how regions of the human genome containing the risk alleles alter the function of the immune system and in doing so, increases an individual’s risk of developing MS.