Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Human Disease Variation in the Light of Population Genomics

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  4. Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Drug-Driven Phenotypic Convergence Supports Rational Treatment Strategies of Chronic Infections

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Early Intrathecal T Helper 17.1 Cell Activity in Huntington Disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Intoxicationer og ernæringsdeficit

    Publikation: Bidrag til bog/antologi/rapportBidrag til bog/antologiUndervisning

  3. Klinisk Neurologi og Neurokirurgi

    Publikation: Bog/antologi/afhandling/rapportBogUndervisning

Vis graf over relationer

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 substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS.

OriginalsprogEngelsk
TidsskriftCell
Vol/bind175
Udgave nummer6
Sider (fra-til)1679-1687.e7
ISSN0092-8674
DOI
StatusUdgivet - 29 nov. 2018

ID: 56321125