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Sökning: WFRF:(Magnusson P) > Annan publikation

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  • Klaric, Lucija, et al. (författare)
  • Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
  • 2021
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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4.
  • Lagerkvist, C.-I., et al. (författare)
  • 1995 GY7
  • 1995
  • Ingår i: 1995MPEC....M...02L.
  • Annan publikation (övrigt vetenskapligt/konstnärligt)
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5.
  • Warstedt, Kristina, 1962-, et al. (författare)
  • Omega-3 long chain polyunsaturated fatty acid supplementation in pregnancy and lactation and immune components in breast milk
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Human milk transfers important immunological information from mother to child. We have previously reported lower prevalence of IgE-mediated disease at 12 months after maternal supplementation with ω-3 long chain polyunsaturated fatty acid (LCPUFA) during pregnancy and lactation. Our aim was to explore the effect of ω-3 LCPUFA on the immune composition of human milk in relation to maternal atopy and allergic disease in the offspring. Pregnant women in families with a history of allergic disease were supplemented daily with 2.7 g ω-3 LCPUFA or 2.8 g soybean oil as placebo from late pregnancy to three months of lactation. Milk samples from colostrum (n=107), at 1 mo (n=102) and at 3 mo (n=95) were analyzed for IL-1ß, IL-2, IL-4, IL-5, IL-6, CXCL-8, IL-10, IL-12p40/p70, IL-13, GM-CSF, TNF, IFN-γ, PGE2, TSLP, TGF-ß2 and SIgA with multiplex assay or ELISA. The levels of several cytokines were higher in non-atopic ω-3 supplemented mothers as compared to placebo supplemented mothers regardless of atopic status. Higher levels of TGFß2 and SIgA in 3 months milk were associated with allergic disease at one year of age both with and without detectable IgE. These results suggest that ω-3 LCPUFA supplementation during pregnancy influences cytokine levels in breast milk especially in non-atopic mothers.
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