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Träfflista för sökning "WFRF:(Rasmussen Katrine L.) "

Sökning: WFRF:(Rasmussen Katrine L.)

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1.
  • Surendran, Praveen, et al. (författare)
  • Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
  • 2020
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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2.
  • Shi, Liu, et al. (författare)
  • Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.
  • 2020
  • Ingår i: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 77:3, s. 1353-1368
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes.We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677).We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts.Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo.
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3.
  • Davies, Siwan M, et al. (författare)
  • Identification of the Fugloyarbanki tephra in the NGRIP ice-core: a key tie-point for marine and ice-core sequences during the last glacial period
  • 2008
  • Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 23:5, s. 409-414
  • Tidskriftsartikel (refereegranskat)abstract
    • A visible tephra horizon in the NGRIP ice core has been identified by geochemical analysis as the Fugloyarbanki Tephra, a widespread marker horizon in marine cores from the Faroe Islands area and the northern North Atlantic. An age of 26 740 ± 390 yr b2k (1σ uncertainty) is derived for this tephra according to the new Greenland Ice Core Chronology (GICC05) based on multi-parameter counting of annual layers. Detection of this tephra for the first time within the NGRIP ice core provides a key tie-point between marine and ice-core records during the transition between MIS 3 and 2. Identification of this volcanic event within the Greenland records demonstrates the future potential of using tephrochronology to precisely correlate palaeoarchives in widely separated localities that span the last glacial period, as well as providing a potential method for examining the extent of the radiocarbon marine reservoir effect at this time.
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