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Low frequency and rare coding variation contributes to multiple sclerosis risk

Multiple sclerosis is a common, complex neurological disease, where almost 20% of risk heritability can be attributed to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that the majority of the remaining heritability is also due to the additive effects of individual variants, rather than epistatic interactions between these variants, or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that as much as 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, which highlight a key role for regulatory T cell homeostasis and regulation, IFNγ biology and NFκB signaling in MS pathogenesis.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00010002019 Illumina 26067
EGAD00010002020 Illumina 2257
EGAD00010002021 Illumina 195
EGAD00010002022 Illumina 896
EGAD00010002023 Illumina 624
EGAD00010002024 Illumina 13632
Publications Citations
Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk.
Cell 175: 2018 1679-1687.e7