Epub: O'Gorman C, Lin R, Stankovich J, Broadley SA. Modelling Genetic Susceptibility to Multiple Sclerosis with Family Data. Neuroepidemiology. 2012; 40:1-12.
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.
This tells us what we already know that there the major genetic susceptibility factor is the major histocompatibility complex and there are many other genes that are a minor part of the risk process, which also has an environmental influence.
Labels: Epidemiology, MS Genes