title: A rare variant of the TYK2 gene is confirmed to be associated with multiple sclerosis.
abstract: A rare functional variant within the TYK2 gene (rs34536443) has been reported as protective in multiple sclerosis (MS) in recent studies. However, because of the low frequency of the minor allele (minor allele frequency=0.04), genome-wide significant association has been hard to establish. We genotyped 5429 Nordic MS cases and 6167 healthy controls for this TYK2 non-synonymous single-nucleotide polymorphism (ns-SNP), and combined the Nordic genotype data with raw genotypes from previous studies. The combined Nordic analysis showed significant association with MS (P=5 x 10(-4), odds ratio (OR) 0.78), and by mega-analysis of 10 642 MS patients, 10 620 controls and 2110 MS trios, the association at genome-wide significance level (P=5.08 x 10(-9), OR 0.77) was shown.
authors.affiliation: Department of Neurology, Oslo University Hospital, Ullevål, N-0407 Oslo, Norway. ilmero@rr-research.no
authors.forename: Inger-Lise
authors.initials: IL
authors.lastname: Mero
authors.forename: Aslaug R
authors.initials: AR
authors.lastname: Lorentzen
authors.forename: Maria
authors.initials: M
authors.lastname: Ban
authors.forename: Cathrine
authors.initials: C
authors.lastname: Smestad
authors.forename: Elisabeth G
authors.initials: EG
authors.lastname: Celius
authors.forename: Jan H
authors.initials: JH
authors.lastname: Aarseth
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.forename: Jenny
authors.initials: J
authors.lastname: Link
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kockum
authors.forename: Thomas
authors.initials: T
authors.lastname: Masterman
authors.forename: Annette Bang
authors.initials: AB
authors.lastname: Oturai
authors.forename: Helle Bach
authors.initials: HB
authors.lastname: Søndergaard
authors.forename: Finn
authors.initials: F
authors.lastname: Sellebjerg
authors.forename: Janna
authors.initials: J
authors.lastname: Saarela
authors.forename: Anu
authors.initials: A
authors.lastname: Kemppinen
authors.forename: Irina
authors.initials: I
authors.lastname: Elovaara
authors.forename: Anne
authors.initials: A
authors.lastname: Spurkland
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
authors.forename: Benedicte A
authors.initials: BA
authors.lastname: Lie
authors.forename: Hanne F
authors.initials: HF
authors.lastname: Harbo
mesh_terms: D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053634:TYK2 Kinase / Q000235:genetics*
chemical_list: D053634:TYK2 Kinase; C070139:TYK2 protein, human