Genetics Research
rs34536443
Population Frequencies10
African
G 0.9926C 0.0074GG 0.985269GC/CG 0.014731CC 0pop=7,060
African American
G 0.9923C 0.0077GG 0.984679GC/CG 0.015321CC 0pop=6,788
Asian
G 0.9997C 0.0003GG 0.999402GC/CG 0.000598CC 0pop=3,346
European
G 0.958102C 0.041898GG 0.917924GC/CG 0.080356CC 0.00172pop=101,150
Latin American 1
G 0.987C 0.013GG 0.974886GC/CG 0.025114CC 0pop=876
Latin American 2
G 0.9864C 0.0136GG 0.972835GC/CG 0.027165CC 0pop=1,178
Other
G 0.9703C 0.0297GG 0.942257GC/CG 0.056073CC 0.00167pop=8,382
Other Asian
G 0.998C 0.002GG 0.996988GC/CG 0.003012CC 0pop=664
South Asian
G 0.978C 0.022GG 0.956835GC/CG 0.043165CC 0pop=278
Studies20
Unread Studies20 ▼
1
Little is known about the causes of serum aquaporin 4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (AQP4-positive NMOSD) or how its pathophysiology differs from other demyelinating autoimmune diseases, which limits therapeutic and preventative opportunities despite available diagnostic biomarkers. By performing a pan-ancestry genome-wide association study (GWAS), we aimed to deepen our understanding of the genetic architecture of AQP4-positive NMOSD and to explore shared herit…
2
Genetic susceptibility to psoriasis involves multiple loci, including TYK2 (Tyrosine Kinase 2), which is associated with various autoimmune diseases. However, its specific role and mechanisms in psoriasis remain unclear. This study aimed to identify psoriasis-associated proteins using Summary-based Mendelian Randomization (SMR) and to explore their regulatory mechanisms. SMR analysis integrating pQTL data was conducted to identify proteins linked to psoriasis, revealing ICAM1 (Intercellular Adhe…
3
The TYK2:p.Pro1104Ala (rs34536443) hypomorph variant has been associated with protection against numerous autoimmune disorders. Thus, its mechanism of action becomes of great interest. Here, consistent with the participation of activated immune cells in autoimmunity, we show that the variant regulates the levels of immune cells at a human, general population level and is associated particularly with higher levels of T and B lymphocytes, especially the naïve (non-activated) compartment. Also…
4
Though genes are already known to be responsible for type 1 diabetes mellitus (T1DM), the knowledge of missense mutation of that disease gene has still to be under covered. A genomic database and a bioinformatics-based approach are integrated in the present study in order to address this issue. Initially, nine variants associated with T1DM were retrieved from the GWAS catalogue. Different genomic algorithms such as PolyPhen2.0, SNPs and GTEx analyser programs were used to study the structural an…
5
Systemic lupus erythematosus (SLE) is an inflammatory-autoimmune disease with a complex multi-organ pathogenesis, and it is known to be associated with significant morbidity and mortality. Various genetic, immunological, endocrine, and environmental factors contribute to SLE. Genomic variants have been identified as potential contributors to SLE susceptibility across multiple continents. However, the specific pathogenic variants that drive SLE remain largely undefined. In this study, we sought t…
6
To explore the associations of genetically proxied TYK2 inhibition with a wide range of disease outcomes and biomarkers to identify therapeutic repurposing opportunities, adverse effects, and biomarkers of efficacy. The loss-of-function missense variant rs34536443 in TYK2 gene was used as a genetic instrument to proxy the effect of TYK2 inhibition. A phenome-wide Mendelian randomization (MR) study was conducted to explore the associations of genetically-proxied TYK2 inhibition with 1473 disease…
7
Multiple Sclerosis (MS) is an autoimmune and central nervous system disease characterized by an inflammatory demyelinating process in the brain. Although the exact cause of MS is still unclear, environmental, and genetic factors are known to play a role in the development of disease. New molecular markers must be identified to understand the mechanism of disease formation and progression. We investigated the effects of MS-related non-synonymous single-nucleotide polymorphisms (nsSNPs) on the str…
8
Deucravacitinib, a novel, selective inhibitor of TYK2 is currently under review at the FDA and EMA for treatment of moderate-to-severe plaque psoriasis. It is unclear whether recent safety concerns (ie, elevated rates of lung cancer and lymphoma) related to similar medications (ie, other JAK inhibitors) are shared with this novel TYK2 inhibitor. We used a partial loss-of-function variant in TYK2 (rs34536443), previously shown to protect against psoriasis and other autoimmune diseases, to evaluat…
9
To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and ~1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). We found 25 sequence variants for RA overall,…
10
Single-nucleotide polymorphisms (SNPs) are reported to be associated with many diseases, including autoimmune diseases. In rheumatoid arthritis (RA), about 152 SNPs are reported to account for ~15% of its heritability. These SNPs may result in the alteration of gene expression and may also affect the stability of mRNA, resulting in diseased protein. Therefore, in order to predict the underlying mechanism of these SNPs and identify novel therapeutic sites for the treatment of RA, several bioinfor…
11
Autoimmune diseases are characterized by the loss of self-tolerance, leading to immune-mediated tissue destruction and chronic inflammation. Tyrosine kinase 2 (TYK2) protein plays a key role in immunity and apoptosis pathways. Studies have reported associations between single nucleotide polymorphisms (SNPs) in the TYK2 gene and autoimmune diseases; however, results are still inconclusive. Thus, we conducted a systematic review followed by meta-analysis. A literature search was performed to find…
12
Type I interferon (IFN-I) pathway plays a central role in the systemic lupus erythematosus (SLE) pathogenesis. Recent data suggest that SLE is associated with variants in IFN-I genes, such as tyrosine kinase 2 (TYK2), which is crucial in anti-viral immunity. Here, five TYK2 single nucleotide polymorphisms (SNPs) were genotyped in 368 childhood-onset SLE Mexican patients and 516 sex-matched healthy controls. Allele frequencies were also estimated in four indigenous groups. SLE protection was asso…
13
Although genome-wide association studies (GWAS) have identified approximately 100 loci for rheumatoid arthritis (RA), the disease mechanisms are not completely understood. We evaluated the pathogenesis of RA by focusing on rare coding variants. The coding regions of 98 candidate genes identified by GWAS were sequenced in 2294 patients with RA and 4461 controls in Japan. An association analysis was performed using cases and controls for variants, genes and domains of TYK2. Cytokine responses for…
14
Rheumatoid Arthritis (RA) is a debilitating disorder in which the immune system mainly targets the synovial tissue. Janus kinase family including tyrosine kinase 2 (TYK2) is one of the crucial mediators of the downstream signaling pathway of inflammatory cytokines that further contributes to RA pathogenesis. In this study, the association of TYK2 gene rs34536443 polymorphism, which may affect the function of TYK protein and, hence, the inflammatory settings, with RA susceptibility was investigat…
15
TYK2 is a JAK family member that functions downstream of multiple cytokine receptors. Genome wide association studies have linked a SNP (rs34536443) within TYK2 encoding a Proline to Alanine substitution at amino acid 1104, to protection from multiple autoimmune diseases including systemic lupus erythematosus (SLE) and multiple sclerosis (MS). The protective role of this SNP in autoimmune pathogenesis, however, remains incompletely understood. Here we found that T follicular helper (Tfh) cells,…
16
Tyrosine kinase 2 (TYK2) belongs to the Janus kinase (JAK) family of tyrosine kinases, which transmit signals from activated cytokine receptors. GWAS have consistently implicated TYK2 in psoriasis susceptibility. We performed an in-depth association analysis of TYK2 using GWAS and resequencing data. Strong genetic association of three nonsynonymous variants in the exonic regions of the TYK2 gene (rs34536443, rs12720356, and rs2304256) were found. rs12720356 encoding I684S is predicted to be dele…
17
The tyrosine kinase 2 protein (Tyk2), encoded by the TYK2 gene, has a crucial role in signal transduction and the pathogenesis of many diseases. A single nucleotide polymorphism of the TYK2 gene, SNP rs34536443, is of major importance, since it has been shown to confer protection against various, mainly, autoimmune diseases. This polymorphism results in a Pro to Ala change at amino acid position 1104 of the encoded Tyk2 protein that affects its enzymatic activity. However, the details of the und…
18
Juvenile idiopathic arthritis (JIA) is an autoimmune disease that is characterized by persistent chronic arthritis and affected by genetic and environmental factors. Different genetic variations have been reported as risk factors for JIA. However, given that many results could not be replicated in individuals of different ancestral origin, it was assumed that heterogeneous genetic factors are involved in this disease. In the present study, we analyzed three single nucleotide polymorphisms (SNPs)…
19
Several rheumatoid arthritis (RA) susceptibility loci have also been found to be associated with psoriatic arthritis (PsA), demonstrating that there is a degree of genetic overlap between various autoimmune diseases. We sought to investigate whether single nucleotide polymorphisms (SNPs) mapping to previously reported RA and/or PsA susceptibility loci, including PLCL2, CCL21, REL, STAT4, CD226, PTPN22, and TYK2, are associated with risk for the two diseases in a genetically homogeneous Greek pop…
20
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 pol…
Curated Studies0 ▼
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