Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk.

ABSTRACT: Multiple sclerosis is a complex neurological disease, with ∼20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that up to 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common-variant signals, highlighting key pathogenic roles for regulatory T cell homeostasis and regulation, IFNγ biology, and NFκB signaling. As low-frequency variants do not show substan

SUBMITTER: International Multiple Sclerosis Genetics Consortium. Electronic address: [e-mail] 

PROVIDER: S-EPMC6269166 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature