indirect evidence that many more common variants of small effect contribute to genetic susceptibility for multiple sclerosis. Simple models, in which the previously known and newly identified variants affect risk multiplicatively, both within and across loci, explain a meaningful proportion (~20%, see Supplementary Information) of genetic risk for the disease
There has long been a link (albeit perhaps a weak one) associating genetics to MS
Within the MHC we have refined the identity of the HLA-DRB1 risk alleles…….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
The model also suggests that HLA DRB1 may not be as uniquely important for MS-susceptibility as currently believed.
Thus, this allele is only one among a hundred or more loci involved in MS susceptibility. Even though the "frequency of susceptibility" at the HLA DRB1 locus is four-fold that of other loci, the penetrance of those susceptible genotypes that include this allele is no different from those that don't.
Also, almost 50% of genetically-susceptible individuals, lack this allele. Moreover, of those who have it, only a small fraction (≤ 5.2%) are even susceptible to getting MS.
…They also identified 29 new genetic variants associated with MS risk albeit with small effects (as well as five variants with a suspected association with MS).
in a study by the International Multiple Sclerosis Genetics Consortium, the classic MS risk locus, HLA-DRB1, stood out with remarkably strong statistical significance, but they also identified 12 other loci and/or genes associated with MS. However, all of these alleles have a very modest odds ratio and they explain approximately 3% of the variance in MS risk.
The collective effect of 12,627 SNPs…..in our discovery GWAS set optimally explains approximately 3% of the variance in MS risk in our independent target GWAS set, suggest that the risk alleles identified to date represent just the tip of an iceberg of risk variants likely to include hundreds of modest effects and possibly thousands of very small effects
We found no evidence for genetic associations with clinical course, severity of disease or month of birth, and no evidence of interaction with gender or DRB1*15:01 in any part of the genome
Most of the genes implicated in the study were related to immune function, and more than one-third have previously been confirmed to be associated with autoimmune diseases. In a second study published in PLoS Genetics (2011;7),
That the media picks up a black and white interpretation and perhaps accentuates it further may simply be a part of the media process.
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