SynthesisAnnals of the rheumatic diseases2016
Influence of TYK2 in systemic sclerosis susceptibility: a new locus in the IL-12 pathway.
Synthesis in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling.Human molecular genetics · 2017Pooled it
- Unfolding the pathogenesis of scleroderma through genomics and epigenomics.Journal of autoimmunity · 2017Pooled it
- Transethnic meta-analysis identifiesAnnals of the rheumatic diseases · 2017Pooled it
- Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease.eLife · 2026Article
- How Genomic and Structural Context Could Shape JAK-STAT Variant Pathogenicity.Twin research and human genetics : the official journal of the International Society for Twin Studies · 2026Article
- Deucravacitinib in dermatology: current indication and existing off-label data.Drugs in context · 2026Review
- IL-12 family cytokines and autoimmune diseases: A potential therapeutic target?Journal of translational autoimmunity · 2025Review
- Review
- Human hypofunctional NCF1 variants promote pulmonary fibrosis in the bleomycin-induced mouse model and patients with systemic sclerosis via expansion of SPP1Annals of the rheumatic diseases · 2025Article
- TYK2 rs34536443 (P1104A) Variant Suppresses ICAM1-Mediated Inflammation: Insights From Mendelian Randomization and Functional Analyses.Psoriasis (Auckland, N.Z.) · 2025Article
- Immunogenetics of Systemic Sclerosis.Genes · 2024Review
- TYK2: an emerging therapeutic target in rheumatic disease.Nature reviews. Rheumatology · 2024Review
- Article
- A novel highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2) can block inflammation- and autoimmune-related pathways.Cell communication and signaling : CCS · 2023Article
- Skin Gene Expression Profiles in Systemic Sclerosis: From Clinical Stratification to Precision Medicine.International journal of molecular sciences · 2023Review
- Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor.Protein & cell · 2023Article
- CXCL4-RNA Complexes Circulate in Systemic Sclerosis and Amplify Inflammatory/Pro-Fibrotic Responses by Myeloid Dendritic Cells.International journal of molecular sciences · 2022Article
- Immune disease risk variants regulate gene expression dynamics during CD4Nature genetics · 2022Article
- Systemic Sclerosis: From Pathophysiology to Novel Therapeutic Approaches.Biomedicines · 2022Review
- The Immunogenetics of Systemic Sclerosis.Advances in experimental medicine and biology · 2022Article
Corrections and comments
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Authors and funding
30 authors at 19 institutions in 6 countries.
Funding
Abstract
objectivesTYK2 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.
methodsThis 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.
resultsGenome-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 allelic combination analyses showed that the strong association observed for V362F with SSc, corresponded to a synthetic association dependent on the effect of the three previously mentioned TYK2 missense variants.
conclusionsWe report for the first time the association of TYK2 with SSc and reinforce the relevance of the IL-12 pathway in SSc pathophysiology.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.