A genetic contribution to susceptibility is well established in multiple sclerosis (MS) and 57 associated genetic loci have been identified. We have undertaken a meta-analysis of familial risk studies with the aims of providing definitive figures for risks to relatives, performing a segregation analysis and estimating the proportion of the overall genetic risk that currently identified genes represent. We have used standard methods of meta-analysis combined with novel approaches to age adjustment to provide directly comparable estimates of lifetime risk. The overall recurrence risk for monozygotic twins (identical twins) was 18.2% and for siblings (brothers and sisters) 2.7%. The recurrence risk for dizygotic twins (non-identical twins) was significantly higher than for siblings. The overall estimate of sibling relative risk (λ(S)) was 16.8. Risks for older relatives (parents, siblings, aunts, uncles and cousins) show a latitudinal gradient, in line with population risk. No latitudinal gradient for λ(S) was seen. Segregation analysis supports a multiplicative model of one locus of moderate effect (probably the major histocompatibility complex) with many loci of small effect. The estimated contribution of the 57 known MS loci is 18-24% of λ(S). This meta-analysis supports the notion of MS being in part the result of multiple genetic susceptibility factors and environmental factors.
Epub: O’Gorman C, Lin R, Stankovich J, Broadley SA. Modelling Genetic Susceptibility to Multiple Sclerosis with Family Data. Neuroepidemiology. 2012; 40:1-12.