Uncovering the genetic architecture of multiple sclerosis

Multiple sclerosis (MS) is a disease in which genetic, environmental, and stochastic factors interact to trigger an inflammatory disease of the CNS that also has a neurodegenerative component. Over the past 3 years, progress in high-throughput technologies and analysis methods has synergized with the collaborative efforts of investigators studying MS genetics to enable the discovery of more than a dozen genes involved in making individuals susceptible to MS. These genes are beginning to suggest molecular pathways that may be particularly vulnerable to genetic variation in MS. Soon, a comprehensive map of common genetic variants affecting MS susceptibility will be assembled, and communal efforts will need to focus on the more challenging issue of understanding the genetic architecture of disease course and treatment response in MS. Early efforts integrating different dimensions of information, including genomics, imaging, transcriptomics, and proteomics, with precise phenotypic data from clinicians illustrate the way forward for prognostic algorithms in MS and suggest that these approaches will yield a new series of insights in the next decade.