Epidemiological observations regarding certain population-wide parameters (eg, disease-prevalence, recurrence-risk in relatives, gender predilections, and the distribution of common genetic-variants) place important constraints on the possibilities for the genetic-basis underlying susceptibility to multiple sclerosis (MS), according to researchers. It is possible, they observed in a recent study, to distinguish between 2 classes of persons, indicating either that multiple sclerosis can be caused by 2 fundamentally different pathophysiological mechanisms or that the large majority of the population is not at risk of developing MS, regardless of their environmental experience. Using a mathematical model to help elucidate the nature and magnitude of these constraints, they found:

• For MS, no more than 8.5% of the population can possibly be in the “genetically-susceptible” subset.

• The expected MS-probability for this subset is more than 12 times than that for everyone not in this subset.

• Provided that genetically susceptible persons (genotypes) who carry the MS susceptibility allele are equally or more likely to get MS than those susceptible persons who don’t carry this allele, then at least 84% of MS-cases must come from this “genetically susceptible” subset.

Citation: Goodin DS. The nature of genetic susceptibility to multiple sclerosis: constraining the possibilities. [Published online ahead of print April 27, 2016]. BMG Neurol. doi:10.1186/s12883-016-0575-6.