Genetic Study of Multiple Sclerosis Yields 29 New Susceptibility Genes Implicating an Immune Mediated Pathogenesis

by Dr Sam Girgis on August 18, 2011

Multiple sclerosis (MS) is an inflammatory disorder that results in a variety of neurological signs and symptoms that can eventually progress to complete disability and death.  The disease is caused by destruction and breakdown of the myelin sheath that covers the nerve axons in the brain and spinal cord.  This process is called demyelination and results in damage to the nerves and dysfunction in the neurological processes that they control.  Almost any neurological symptoms can be a manifestation of MS, and the onset of symptoms usually occurs in young adults in the twenties or thirties.  Previous studies have suggested a genetic immune mediated etiology for the disease with environmental contributors at the onset which incite the autoimmune phenomenon.  Researchers working with The International Multiple Sclerosis Genetics Consortium and The Wellcome Trust Case Control Consortium 2 have found 29 new susceptibility genes that have implicated an immune mediated pathogenesis for MS.  The results of their study were published online in the journal Nature.  The international team of researchers performed a genome wide association study involving 9,772 cases of MS of European descent that were collected by 23 research groups in 15 different countries.  There were 17,376 controls used in the study that did not have MS.  The researchers were able to confirm 23 genes that were previously identified to contribute to the pathogenesis of MS.  In addition, the researchers identified 29 additional gene loci that may contribute to the etiology of the disease.  More than one third of the newly identified genes were shown to overlap with genetic regions that have been implicated in other autoimmune disorders such as rheumatoid arthritis, Crohn’s colitis, and type 1 diabetes mellitus.  Many of the 29 newly identified genes are involved in T lymphocyte function, activation, and differentiation.  In addition, there are many genes involved in T lymphocyte cell surface receptors as well as receptors for the major histocompatibility complex.  These findings add to the already existent database implicating an immune mediated pathogenesis for the development of MS.  The authors of the study wrote, “Twenty three of the 26 previously known or strongly suggested multiple-sclerosis associated loci were replicated in our primary [genome wide association study]… Our [genome wide association study] and replication also revealed another 29 novel associated regions… Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis”.  Future studies with evaluate the individual contributions of the identified genes in the etiology of multiple sclerosis and may help in the development of more effective medications to treat this severely debilitating disorder.


Stephen Sawcer et al. “Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis” Nature 476, 214-219 published online August 11, 2011 doi:10.1038/nature10251

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