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Modelling genetic susceptibility to multiple sclerosis with family data
journal contribution
posted on 2023-05-17, 18:22 authored by O'Gorman, C, Lin, R, Jim Stankovich, Broadley, SAA 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 was 18.2% and for siblings 2.7%. The recurrence risk for dizygotic twins was significantly higher than for siblings. The overall estimate of sibling relative risk (λS) 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 λS was seen. Segregation analysis supports a multiplicative model of one locus of moderate effect with many loci of small effect. The estimated contribution of the 57 known MS loci is 18-24% of λS. This meta-analysis supports the notion of MS being in part the result of multiple genetic susceptibility factors and environmental factors.
History
Publication title
NeuroepidemiologyVolume
40Pagination
1-12ISSN
0251-5350Department/School
Menzies Institute for Medical ResearchPublisher
KargerPlace of publication
Allschwilerstrasse 10, Basel, Switzerland, Ch-4009Rights statement
Copyright 2013 S. Karger AG, BaselRepository Status
- Restricted