From genetic associations to functional studies in multiple sclerosis

Genetic screens steadily reveal more loci that show robust associations to complex human diseases, including multiple sclerosis (MS). Although some of the identified genetic variants are easily interpreted into a biological function, most of the genetic associations are frequently challenging to interpret. Underlying these difficulties is the fact that chip-based assays typically detect single nucleotide polymorphisms (SNPs) representative of a stretch of DNA containing many genomic variants in linkage disequilibrium. Furthermore, a large proportion of the SNPs with strongest association to MS are located in regions of the DNA that do not directly code for proteins. Here we discuss challenges faced by MS researchers to follow up the large-scale genetic screens that have been published over the past years in search of functional consequences of the identified MS-associated SNPs. We discuss experimental design, tools and methods that may provide the much-needed biological insights in both disease etiology and disease manifestations.