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Published on: June 21, 2018
Genetic burden in multiple sclerosis families
N Isobe1, V Damotte1,2, V Lo Re3
1Department of Neurology, University of California at San Francisco, San Francisco, CA, USA.
Genes and Immunity
|August 2, 2013
Summary
Genetic risk scores help track multiple sclerosis (MS) susceptibility variants in families. While updated markers improve accuracy, predicting MS remains challenging, though genetic architectures for different MS types appear similar.
Area of Science:
- Genetics
- Neuroimmunology
- Epidemiology
Background:
- Previous studies estimated genetic risk in multiple sclerosis (MS) using limited susceptibility loci (17 loci).
- The complete set of MS risk genes is not yet fully identified.
- Genetic burden aggregation in families is a known factor in MS heritability.
Purpose of the Study:
- To estimate the genetic burden in multiple sclerosis (MS) families using an expanded set of single-nucleotide polymorphism (SNP) markers (64 SNPs).
- To assess the predictive power of genetic burden for MS development, even within sibling groups.
- To investigate the shared genetic architecture between primary progressive and relapsing-remitting forms of MS.
Main Methods:
- Genotyping of 708 controls, 3251 MS patients and relatives, and 117 twin pairs.
- Calculation of cumulative genetic risk scores using up to 64 SNP markers based on recent literature.
- Statistical analysis to compare genetic burden aggregation in multi-case versus single-case families and assess predictive accuracy (AUROC).
Main Results:
- Validated increased aggregation of genetic burden in multi-case compared to single-case families (P=4.14e-03).
- Limited predictive power for MS, even within sibships (AUROC=0.59).
- Suggests a common genetic architecture for primary progressive and relapsing-remitting MS (P=0.368).
- Integration of new GWAS and meta-analysis findings corrects previous MS genetic risk estimations.
Conclusions:
- Updated genetic risk scores confirm increased genetic burden aggregation in MS families.
- Current genetic markers offer minimal accuracy for predicting MS onset, even in high-risk individuals.
- The genetic basis for different clinical forms of MS is largely shared, indicating common underlying susceptibility factors.
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