Unravelling the complex genetics of Multiple Sclerosis

 

Multiple Sclerosis (MS) is the most common cause of non-traumatic neurological disability affecting young adults. Relatively little is known about the genetics of MS although a polygenic, multifactorial model of inheritance is implicated by epidemiological and genome-wide association studies. Prior to a recent collaborative study led by researchers at the University of California, San Francisco and Harvard Medical School, only a fraction of disease-related loci had been uncovered. The results of this new analysis were this week published by Genome Medicine.

In this study, Oksenberg and colleagues built upon the existing dataset and used logistic regression methodology to identify novel candidate genes associated with MS susceptibility.  The resulting genetic profile showed a significant enrichment of genes involved in the immune response, nervous system development and neuronal signaling. Interestingly, members of the glutamate-receptor family were identified as risk alleles, although their contribution to MS etiology remains to be determined.

Altogether, around 350 independent variants were identified as accounting for a significant fraction of the genetic component of MS. These results lend further support to the polygenic model of inheritance and pave the way for follow-up studies that assess the role of the environment in modulating heritability.

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