Multiple sclerosis genetics is dead

This review addresses several areas of contention related to the genetic theory for multiple sclerosis (MS). It is argued (a) that the concept of MS as a ‘complex disease’ has little value, (b) just because a disorder is found in multiple families, it is not necessarily genetically based, (c) although twin studies are claimed to show that MS is ‘30% genetically based’ this concept derives from widely varying data, (d) although genome-wide association studies (GWAS) suggest the presence of several MS related genes this has yet to be proven, (e) monozygotic twins discordant for MS should have a different genetic sequence if the disorder has a genetic basis but data so far suggest this may not be correct and (f) epigenetics or epistasis are contentious topics and may not provide the answer. It is concluded that the role of genetics in MS etiology may be overstated and that attention should now be devoted to environmental causes.

► The term ‘complex disease’ has no useful meaning and should not be used.
► Multicase pedigrees do not necessarily have a primary genetic basis.
► Classic twin studies MS are inconclusive.
► GWAS have not isolated any mutations for MS, unlike familial parkinsonism.
► The words ‘epigenetic’ and ‘epistasis’ are speculative processes for MS.
► The balance of current evidence does not support a major genetic role in MS.