TYK2 as a novel therapeutic target in psoriasis

Elyoussfi, Sarah; Rane, Shraddha S; Eyre, Steve; Warren, Richard B

doi:10.1080/17512433.2023.2219054

Cited by 4 publications

(1 citation statement)

References 79 publications

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“…Rs34536443 is a loss-of-function missense variant (p.Pro1104Ala) for TYK2 and the functionally impairing minor C allele was associated with a 50% increased risk for severe COVID-19 (odds ratio: 1.50; 95%-CI: 1.40– 1.62, p -value = 4.3 x 10 −29 ) but a 23% reduced risk for rheumatoid arthritis (odds ratio: 0.77; 95%-CI: 0.72–0.83; p -value = 2.4 x 10 −12 ) as well as other autoimmune diseases, in particular psoriasis (Supplementary Data 8 ). While the discrepancy between the success of the drug and genetic inference might be explained by the rather weak affinity of baricitinib for TYK2 33 , patients undergoing trials with TYK2-inhibitors for psoriasis 34 might be at an elevated risk for severe COVID-19. This observation seemingly aligns with studies on Tyk2 -/- mouse models reporting an impaired immune response to viral infections 35 .…”

Section: Resultsmentioning

confidence: 99%

Complex patterns of multimorbidity associated with severe COVID-19 and long COVID

Pietzner,

Denaxas,

Yasmeen

et al. 2024

Commun Med

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Background Early evidence that patients with (multiple) pre-existing diseases are at highest risk for severe COVID-19 has been instrumental in the pandemic to allocate critical care resources and later vaccination schemes. However, systematic studies exploring the breadth of medical diagnoses are scarce but may help to understand severe COVID-19 among patients at supposedly low risk. Methods We systematically harmonized >12 million primary care and hospitalisation health records from ~500,000 UK Biobank participants into 1448 collated disease terms to systematically identify diseases predisposing to severe COVID-19 (requiring hospitalisation or death) and its post-acute sequalae, Long COVID. Results Here we identify 679 diseases associated with an increased risk for severe COVID-19 (n = 672) and/or Long COVID (n = 72) that span almost all clinical specialties and are strongly enriched in clusters of cardio-respiratory and endocrine-renal diseases. For 57 diseases, we establish consistent evidence to predispose to severe COVID-19 based on survival and genetic susceptibility analyses. This includes a possible role of symptoms of malaise and fatigue as a so far largely overlooked risk factor for severe COVID-19. We finally observe partially opposing risk estimates at known risk loci for severe COVID-19 for etiologically related diseases, such as post-inflammatory pulmonary fibrosis or rheumatoid arthritis, possibly indicating a segregation of disease mechanisms. Conclusions Our results provide a unique reference that demonstrates how 1) complex co-occurrence of multiple – including non-fatal – conditions predispose to increased COVID-19 severity and 2) how incorporating the whole breadth of medical diagnosis can guide the interpretation of genetic risk loci.

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Section: Resultsmentioning

confidence: 99%

Complex patterns of multimorbidity associated with severe COVID-19 and long COVID

Pietzner,

Denaxas,

Yasmeen

et al. 2024

Commun Med

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The new era of immune skin diseases: Exploring advances in basic research and clinical translations

Zhang,

Mei,

Zhao

et al. 2024

Journal of Translational Autoimmunity

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Complex patterns of multimorbidity associated with severe COVID-19 and Long COVID

Pietzner,

Denaxas,

Yasmeen

et al. 2023

Preprint

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Many diseases with significant health burden and healthcare costs have been neglected in biomedical research, partly due to a lack of data. Here, we systematically harmonized >12 million primary care and hospitalisation health records from ~440,000 UK Biobank participants into 1445 collated disease terms for genetic analyses. This included ~200 diseases with >10,000 cases that are predominantly managed in primary care, like skin and non-serious infectious diseases. We quantify the heritability for these common diseases, identify novel loci with extreme effect sizes, and highlight novel roles of poorly characterised genes, e.g.PNLIPRP3as a sebaceous gland cell-specific gene for rosacea. We characterise the substantial regional pleiotropy with more than 300 independent genomic regions associated with multiple, often seemingly unrelated diseases and use these insights to generate a pan-genome disease network of shared disease loci to prioritise potential pathways contributing to multiple diseases and onset of multimorbidity. We demonstrate the value of primary care data to improve and guide genetic approaches for drug selection, repurposing, and adverse event prediction, e.g.,IGFR1as a putative multi-disease target for, among others, gout and atrial fibrillation, through network augmentation and integration of molecular quantitative trait loci. We make all results publicly available via an interactive webserver (https://www.omicscience.org/apps/phecodes). Our results provide new insights for diseases across diverse clinical specialties and provide a resource for drug discovery and mechanistic understanding.

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TYK2 as a novel therapeutic target in psoriasis

Cited by 4 publications

References 79 publications

Complex patterns of multimorbidity associated with severe COVID-19 and long COVID

Complex patterns of multimorbidity associated with severe COVID-19 and long COVID

The new era of immune skin diseases: Exploring advances in basic research and clinical translations

Complex patterns of multimorbidity associated with severe COVID-19 and Long COVID

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