A rare variant of the TYK2 gene is confirmed to be associated with multiple sclerosis

Eur J Hum Genet. 2010 Apr;18(4):502-4. doi: 10.1038/ejhg.2009.195. Epub 2009 Nov 4.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Multiple Sclerosis / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • TYK2 Kinase / genetics*


  • TYK2 Kinase
  • TYK2 protein, human