Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor

Maria Ban, An Goris, Åslaug R. Lorentzen, Amie Baker, Tania Mihalova, Gillian Ingram, David R. Booth, Robert N. Heard, Graeme J. Stewart, Elke Bogaert, Bénédicte Dubois, Hanne F. Harbo, Elisabeth G. Celius, Anne Spurkland, Richard Strange, Clive Hawkins, Neil P. Robertson, Frank Dudbridge, James Wason, Philip L. De Jager & 10 others David Hafler, John D. Rioux, Adrian J. Ivinson, Jacob L McCauley, Margaret A Pericak-Vance, Jorge R. Oksenberg, Stephen L. Hauser, David Sexton, Jonathan Haines, Stephen Sawcer

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

In a recent genome-wide association study (GWAS) based on 12374 non-synonymous single nucleotide polymorphisms we identified a number of candidate multiple sclerosis susceptibility genes. Here, we describe the extended analysis of 17 of these loci undertaken using an additional 4234 patients, 2983 controls and 2053 trio families. In the final analysis combining all available data, we found that evidence for association was substantially increased for one of the 17 loci, rs34536443 from the tyrosine kinase 2 (TYK2) gene (P=2.7 × 10-6, odds ratio=1.32 (1.17-1.47)). This single nucleotide polymorphism results in an amino acid substitution (proline to alanine) in the kinase domain of TYK2, which is predicted to influence the levels of phosphorylation and therefore activity of the protein and so is likely to have a functional role in multiple sclerosis.

Original languageEnglish
Pages (from-to)1309-1313
Number of pages5
JournalEuropean Journal of Human Genetics
Volume17
Issue number10
DOIs
StatePublished - Mar 19 2009

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TYK2 Kinase
Multiple Sclerosis
Single Nucleotide Polymorphism
Genome-Wide Association Study
Amino Acid Substitution
Proline
Alanine
Genes
Phosphotransferases
Odds Ratio
Phosphorylation
Proteins

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Ban, M., Goris, A., Lorentzen, Å. R., Baker, A., Mihalova, T., Ingram, G., ... Sawcer, S. (2009). Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor. European Journal of Human Genetics, 17(10), 1309-1313. https://doi.org/10.1038/ejhg.2009.41

Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor. / Ban, Maria; Goris, An; Lorentzen, Åslaug R.; Baker, Amie; Mihalova, Tania; Ingram, Gillian; Booth, David R.; Heard, Robert N.; Stewart, Graeme J.; Bogaert, Elke; Dubois, Bénédicte; Harbo, Hanne F.; Celius, Elisabeth G.; Spurkland, Anne; Strange, Richard; Hawkins, Clive; Robertson, Neil P.; Dudbridge, Frank; Wason, James; De Jager, Philip L.; Hafler, David; Rioux, John D.; Ivinson, Adrian J.; McCauley, Jacob L; Pericak-Vance, Margaret A; Oksenberg, Jorge R.; Hauser, Stephen L.; Sexton, David; Haines, Jonathan; Sawcer, Stephen.

In: European Journal of Human Genetics, Vol. 17, No. 10, 19.03.2009, p. 1309-1313.

Research output: Contribution to journalArticle

Ban, M, Goris, A, Lorentzen, ÅR, Baker, A, Mihalova, T, Ingram, G, Booth, DR, Heard, RN, Stewart, GJ, Bogaert, E, Dubois, B, Harbo, HF, Celius, EG, Spurkland, A, Strange, R, Hawkins, C, Robertson, NP, Dudbridge, F, Wason, J, De Jager, PL, Hafler, D, Rioux, JD, Ivinson, AJ, McCauley, JL, Pericak-Vance, MA, Oksenberg, JR, Hauser, SL, Sexton, D, Haines, J & Sawcer, S 2009, 'Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor', European Journal of Human Genetics, vol. 17, no. 10, pp. 1309-1313. https://doi.org/10.1038/ejhg.2009.41
Ban M, Goris A, Lorentzen ÅR, Baker A, Mihalova T, Ingram G et al. Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor. European Journal of Human Genetics. 2009 Mar 19;17(10):1309-1313. https://doi.org/10.1038/ejhg.2009.41
Ban, Maria ; Goris, An ; Lorentzen, Åslaug R. ; Baker, Amie ; Mihalova, Tania ; Ingram, Gillian ; Booth, David R. ; Heard, Robert N. ; Stewart, Graeme J. ; Bogaert, Elke ; Dubois, Bénédicte ; Harbo, Hanne F. ; Celius, Elisabeth G. ; Spurkland, Anne ; Strange, Richard ; Hawkins, Clive ; Robertson, Neil P. ; Dudbridge, Frank ; Wason, James ; De Jager, Philip L. ; Hafler, David ; Rioux, John D. ; Ivinson, Adrian J. ; McCauley, Jacob L ; Pericak-Vance, Margaret A ; Oksenberg, Jorge R. ; Hauser, Stephen L. ; Sexton, David ; Haines, Jonathan ; Sawcer, Stephen. / Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor. In: European Journal of Human Genetics. 2009 ; Vol. 17, No. 10. pp. 1309-1313.
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