title: Estimating the proportion of variation in susceptibility to multiple sclerosis captured by common SNPs.
abstract: Multiple sclerosis (MS) is a complex disease with underlying genetic and environmental factors. Although the contribution of alleles within the major histocompatibility complex (MHC) are known to exert strong effects on MS risk, much remains to be learned about the contributions of loci with more modest effects identified by genome-wide association studies (GWASs), as well as loci that remain undiscovered. We use a recently developed method to estimate the proportion of variance in disease liability explained by 475,806 single nucleotide polymorphisms (SNPs) genotyped in 1,854 MS cases and 5,164 controls. We reveal that ~30% of MS genetic liability is explained by SNPs in this dataset, the majority of which is accounted for by common variants. These results suggest that the unaccounted for proportion could be explained by variants that are in imperfect linkage disequilibrium with common GWAS SNPs, highlighting the potential importance of rare variants in the susceptibility to MS.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: Corey T
authors.initials: CT
authors.lastname: Watson
authors.forename: Giulio
authors.initials: G
authors.lastname: Disanto
authors.forename: Felix
authors.initials: F
authors.lastname: Breden
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.forename: Sreeram V
authors.initials: SV
authors.lastname: Ramagopalan
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008285:Major Histocompatibility Complex / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D006113:United Kingdom