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Sökning: WFRF:(Macfarlane G)

  • Resultat 1-10 av 65
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1.
  • Thomas, HS, et al. (författare)
  • 2019
  • swepub:Mat__t
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  • Arking, D. E., et al. (författare)
  • Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
  • 2014
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
  • Tidskriftsartikel (refereegranskat)abstract
    • The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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  • Pulit, S. L., et al. (författare)
  • Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
  • 2018
  • Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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  • Thompson, B. B., et al. (författare)
  • The Gaia-ESO Survey : matching chemodynamical simulations to observations of the Milky Way
  • 2018
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 473:1, s. 185-197
  • Tidskriftsartikel (refereegranskat)abstract
    • The typical methodology for comparing simulated galaxies with observational surveys is usually to apply a spatial selection to the simulation to mimic the region of interest covered by a comparable observational survey sample. In this work, we compare this approach with a more sophisticated post-processing in which the observational uncertainties and selection effects (photometric, surface gravity and effective temperature) are taken into account. We compare a 'solar neighbourhood analogue' region in a model Milky Way-like galaxy simulated with RAMSES-CH with fourth release Gaia-ESO survey data. We find that a simple spatial cut alone is insufficient and that the observational uncertainties must be accounted for in the comparison. This is particularly true when the scale of uncertainty is large compared to the dynamic range of the data, e.g. in our comparison, the [Mg/Fe] distribution is affected much more than the more accurately determined [Fe/H] distribution. Despite clear differences in the underlying distributions of elemental abundances between simulation and observation, incorporating scatter to our simulation results to mimic observational uncertainty produces reasonable agreement. The quite complete nature of the Gaia-ESO survey means that the selection function has minimal impact on the distribution of observed age and metal abundances but this would become increasingly more important for surveys with narrower selection functions.
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9.
  • Thompson, B. B., et al. (författare)
  • The Gaia-ESO survey : Matching chemodynamical simulations to observations of the Milky Way
  • 2018
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711. ; 473:1, s. 185-197
  • Tidskriftsartikel (refereegranskat)abstract
    • The typical methodology for comparing simulated galaxies with observational surveys is usually to apply a spatial selection to the simulation to mimic the region of interest covered by a comparable observational survey sample. In this work, we compare this approach with a more sophisticated post-processing in which the observational uncertainties and selection effects (photometric, surface gravity and effective temperature) are taken into account. We compare a 'solar neighbourhood analogue' region in a model MilkyWay-like galaxy simulated with RAMSES-CH with fourth release Gaia-ESO survey data. We find that a simple spatial cut alone is insufficient and that the observational uncertainties must be accounted for in the comparison. This is particularly true when the scale of uncertainty is large compared to the dynamic range of the data, e.g. in our comparison, the [Mg/Fe] distribution is affected much more than the more accurately determined [Fe/H] distribution. Despite clear differences in the underlying distributions of elemental abundances between simulation and observation, incorporating scatter to our simulation results to mimic observational uncertainty produces reasonable agreement. The quite complete nature of the Gaia-ESO survey means that the selection function has minimal impact on the distribution of observed age and metal abundances but this would become increasingly more important for surveys with narrower selection functions.
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