Genetic factors play an important role in determining the risk of multiple 
sclerosis (MS). The strongest genetic association in MS is located within the 
major histocompatibility complex class II region (MHC), but more than 50 MS loci 
of modest effect located outside the MHC have now been identified. However, the 
relative candidate genes that underlie these associations and their functions 
are largely unknown. We conducted a protein-protein interaction (PPI) analysis 
of gene products coded in loci recently reported to be MS associated at the 
genome-wide significance level and in loci suggestive of MS association. Our aim 
was to identify which suggestive regions are more likely to be truly associated, 
which genes are mostly implicated in the PPI network and their expression 
profile. From three recent independent association studies, SNPs were considered 
and divided into significant and suggestive depending on the strength of the 
statistical association. Using the Disease Association Protein-Protein Link 
Evaluator tool we found that direct interactions among genetic products were 
significantly higher than expected by chance when considering both significant 
regions alone (p<0.0002) and significant plus suggestive (p<0.007). The number 
of genes involved in the network was 43. Of these, 23 were located within 
suggestive regions and many of them directly interacted with proteins coded 
within significant regions. These included genes such as SYK, IL-6, CSF2RB, 
FCLR3, EIF4EBP2 and CHST12. Using the gene portal BioGPS, we tested the 
expression of these genes in 24 different tissues and found the highest values 
among immune-related cells as compared to non-immune tissues (p<0.001). A gene 
ontology analysis confirmed the immune-related functions of these genes. In 
conclusion, loci currently suggestive of MS association interact with and have 
similar expression profiles and function as those significantly associated, 
highlighting the fact that more common variants remain to be found to be 
associated to MS.