Influence of TYK2 in systemic sclerosis susceptibility: a new locus in the IL-12 pathway

Annals of the Rheumatic Diseases
Elena López-IsacJavier Martín

Abstract

TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus in SSc. This study comprised a total of 7103 patients with SSc and 12 220 healthy controls of European ancestry from Spain, USA, Germany, the Netherlands, Italy and the UK. Four TYK2 single-nucleotide polymorphisms (V362F (rs2304256), P1104A (rs34536443), I684S (rs12720356) and A928V (rs35018800)) were selected for follow-up based on the results of an Immunochip screening phase of the locus. Association and dependence analyses were performed by the means of logistic regression and conditional logistic regression. Meta-analyses were performed using the inverse variance method. Genome-wide significance level was reached for TYK2 V362F common variant in our pooled analysis (p=3.08×10(-13), OR=0.83), while the association of P1104A, A928V and I684S rare and low-frequency missense variants remained significant with nominal signals (p=2.28×10(-3), OR=0.80; p=1.27×10(-3), OR=0.59; p=2.63×10(-5), OR=0.83, respectively). Interestingly, dependence and al...Continue Reading

References

Feb 1, 1988·Postgraduate Medical Journal·A J BarnettG O Littlejohn
May 8, 2009·The New England Journal of Medicine·Armando GabrielliThomas Krieg
Jan 15, 2010·The New England Journal of Medicine·Christopher E M GriffithsUNKNOWN ACCEPT Study Group
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Apr 13, 2010·Nature Genetics·Timothy R D J RadstakeMaureen D Mayes
Jul 17, 2010·Bioinformatics·Randall J PruimCristen J Willer
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Mar 1, 2011·Brain : a Journal of Neurology·Nicolas CouturierDavid Brassat
Nov 3, 2011·PLoS Genetics·Deborah S Cunninghame GrahamTimothy J Vyse
Jan 6, 2012·Human Genetics·José Ezequiel MartínJavier Martín
Jul 21, 2012·Nature Immunology·Dario A A Vignali, Vijay K Kuchroo
Aug 28, 2012·Human Molecular Genetics·Jason D CooperStephen C L Gough
Sep 11, 2012·Nature Genetics·Jimmy Z LiuUNKNOWN Wellcome Trust Case Control Consortium 3
Jan 15, 2013·BMC Medicine·Shervin AssassiJavier Martin
Jan 30, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhi LiSandra Pellegrini
Apr 23, 2013·Nature Genetics·Jimmy Z LiuUNKNOWN International IBD Genetics Consortium
Jun 12, 2013·Nature Genetics·UNKNOWN International Genetics of Ankylosing Spondylitis Consortium (IGAS)Matthew A Brown
Jul 9, 2013·American Journal of Human Genetics·Güher Saruhan-DireskeneliAmr H Sawalha
Aug 7, 2013·Nature Reviews. Genetics·Miles ParkesMatthew A Brown
Jan 7, 2014·American Journal of Human Genetics·Maureen D MayesJavier Martin
Mar 25, 2014·Expert Opinion on Therapeutic Targets·Yan LiangDong-Qing Ye
Sep 10, 2014·Arthritis & Rheumatology·Elena López-IsacJavier Martin

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Citations

Dec 4, 2015·Cytokine·Nicole R LeitnerMathias Müller
Nov 9, 2016·Current Opinion in Immunology·Kiyoshi HiraharaJohn J O'Shea
Mar 21, 2017·Annals of the Rheumatic Diseases·Chikashi TeraoYannick Allanore
Aug 8, 2020·International Journal of Rheumatic Diseases·Jingjing ChenYahua Wang
Jun 17, 2021·Inflammation and Regeneration·Yuko Ota, Masataka Kuwana

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