Saturday, 31 March 2012

Research:Genetics of Progression

Martinelli-Boneschi et al. A genome-wide association study in progressive multiple sclerosis.Mult Scler. 2012 Mar 28. [Epub ahead of print] 

Background: The role played by genetic factors in influencing the clinical course of multiple sclerosis (MS) is not yet well established.


Objective: We aimed to identify genetic variants associated with progressive MS (PrMS).

Methods: We conducted a genome-wide association study (GWAS) in 197 patients with PrMS and 234 controls of Italian origin. We tested the top 20 single nucleotide polymorphisms (SNPs) with suggestive evidence of association (p-value<10(-4)) in two independent sets of primary progressive MS cases and controls.

Results: We identified a risk-associated SNP in the HLA region in linkage disequilibrium (LD) with DRB1*1501 and DQB*0602 loci, with genome-wide significance (rs3129934(T), p(combined)=6.7×10(-16), OR=2.34, 95% CI=1.90-2.87), and a novel locus on chromosome 7q35 with suggestive evidence of association (rs996343(G), p(combined)=2.4×10(-5), OR=0.70, 95% CI=0.59-0.83) which maps within a human endogenous retroviral (HERV) element. Pathway analyses point to an expression regulation of genes involved in neurodegeneration, including glutamate metabolism (p<0.01) and axonal guidance signalling (p<0.02).

Conclusions: We have confirmed the established association with the HLA region and, despite the low statistical power of the study, we found suggestive evidence for association with a novel locus on chromosome 7, with a putative regulatory role.


We have known about a HLA link to MS for many years. This suggests that there is an immune effect somewhere influencing MS. There have been over 50 over genes, mostly immune associated, linked to the susceptibility to multiple sclerosis. These studies indicate that examining anything less than a few thousand samples generally does not tell us anything concrete. Therefore with less than 500  samples and only ~250 affected anything found in this study is probably dubious. The locus on chromosome 7 maps to HERV...."evidence for the Charcot Project?" They point to genes involved in neurodegeneration, is this because they think that progression links to neurodegeneration. Until more substantial studies are done we will not really know.

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