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Träfflista för sökning "WFRF:(Kanai Y) "

Sökning: WFRF:(Kanai Y)

  • Resultat 1-10 av 57
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  • Wuttke, Matthias, et al. (författare)
  • A catalog of genetic loci associated with kidney function from analyses of a million individuals
  • 2019
  • Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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  • Abdo, A. A., et al. (författare)
  • FERMI DISCOVERY OF GAMMA-RAY EMISSION FROM NGC 1275
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 699:1, s. 31-39
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery of high-energy (E > 100 MeV) gamma-ray emission from NGC 1275, a giant elliptical galaxy lying at the center of the Perseus cluster of galaxies, based on observations made with the Large Area Telescope (LAT) of the Fermi Gamma-ray Space Telescope. The positional center of the gamma-ray source is only approximate to 3' away from the NGC 1275 nucleus, well within the 95% LAT error circle of approximate to 5'. The spatial distribution of gamma-ay photons is consistent with a point source. The average flux and power-law photon index measured with the LAT from 2008 August 4 to 2008 December 5 are F-gamma = (2.10 +/- 0.23) x 10(-7) ph (>100 MeV) cm(-2) s(-1) and Gamma = 2.17 +/- 0.05, respectively. The measurements are statistically consistent with constant flux during the four-month LAT observing period. Previous EGRET observations gave an upper limit of F-gamma < 3.72 x 10(-8) ph (>100 MeV) cm(-2) s(-1) to the gamma-ray flux from NGC 1275. This indicates that the source is variable on timescales of years to decades, and therefore restricts the fraction of emission that can be produced in extended regions of the galaxy cluster. Contemporaneous and historical radio observations are also reported. The broadband spectrum of NGC 1275 is modeled with a simple one-zone synchrotron/synchrotron self-Compton model and a model with a decelerating jet flow.
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  • Malik, R., et al. (författare)
  • Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes
  • 2018
  • Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 50:D, Munich, Germany. [Chauhan, Ganesh] Indian Inst Sci, Ctr Brain Res, Bangalore, Karnataka, India. [Chauhan, Ganesh; Sargurupremraj, Muralidharan; Mishra, Aniket; Tzourio, Christophe; Debette, [Traylor, Matthew; Rutten-Jacobs, Loes; Markus, Hugh S.] Univ Cambridge, Div Clin Neurosci, Stroke [Sargurupremraj, Muralidharan; Mishra, Aniket; Debette, Stephanie] Bordeaux Univ Hosp, Inst [Okada, Yukinori; Kanai, Masahiro; Kamatani, Yoichiro] RIKEN Ctr Integrat Med Sci, Lab Stat Anal, [Okada, Yukinori; Kanai, Masahiro; Sakaue, Saori] Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, [Okada, Yukinori] Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka, [Giese, Anne-Katrin; Rost, Natalia S.] Harvard Med Sch, MGH, Dept Neurol, Boston, MA USA. [van der Laan, Sander W.] Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol,Dept [Gretarsdottir, Solveig; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] DeCODE Genet [Anderson, Christopher D.; Rosand, Jonathan] MGH, Ctr Genom Med, Boston, MA USA. [Anderson, Christopher D.; Ay, Hakan; Rost, Natalia S.; Rosand, Jonathan] MGH, J Philip Kistler Stroke [Anderson, Christopher D.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, s. 524-
  • Tidskriftsartikel (refereegranskat)abstract
    • Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke sub-types. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.
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  • Tin, Adrienne, et al. (författare)
  • Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
  • 2019
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 51:10, s. 1459-1474
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.
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  • Abdo, A. A., et al. (författare)
  • Detection of the energetic pulsar PSR B1509-58 and its pulsar wind nebula in MSH 15-52 using the Fermi-large area telescope
  • 2010
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 714:1, s. 927-936
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the detection of high-energy gamma-ray emission from the young and energetic pulsar PSR B1509-58 and its pulsar wind nebula (PWN) in the composite supernova remnant G320.4-1.2 (aka MSH 15-52). Using 1 yr of survey data with the Fermi-Large Area Telescope (LAT), we detected pulsations from PSR B1509-58 up to 1 GeV and extended gamma-ray emission above 1 GeV spatially coincident with the PWN. The pulsar light curve presents two peaks offset from the radio peak by phases 0.96 +/- 0.01 and 0.33 +/- 0.02. New constraining upper limits on the pulsar emission are derived below 1 GeV and confirm a severe spectral break at a few tens of MeV. The nebular spectrum in the 1-100 GeV energy range is well described by a power law with a spectral index of (1.57 +/- 0.17 +/- 0.13) and a flux above 1 GeV of (2.91 +/- 0.79 +/- 1.35) x 10(-9) cm(-2) s(-1). The first errors represent the statistical errors on the fit parameters, while the second ones are the systematic uncertainties. The LAT spectrum of the nebula connects nicely with Cherenkov observations, and indicates a spectral break between GeV and TeV energies.
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  • Andersson, V., et al. (författare)
  • Large-Area Balloon-Borne Polarized Gamma Ray Observer (PoGO)
  • 2005
  • Ingår i: Proceedings of the 22nd Texas Symposium on Relativistic Astrophysics at Stanford. ; , s. 736-743
  • Konferensbidrag (refereegranskat)abstract
    • We are developing a new balloon-borne instrument (PoGO), to measure polarization of soft gamma rays (30-200 keV) using asymmetry in azimuth angle distribution of Compton scattering. PoGO is designed to detect 10 % polarization in 100mCrab sources in a 6-8 hour observation and bring a new dimension to studies on gamma ray emission/transportation mechanism in pulsars, AGNs, black hole binaries, and neutron star surface. The concept is an adaptation to polarization measurements of well-type phoswich counter consisting of a fast plastic scintillator (the detection part), a slow plastic scintillator (the active collimator) and a BGO scintillator (the bottom anti-counter). PoGO consists of close-packed array of 217 hexagonal well-type phoswich counters and has a narrow field-of-view (~ 5 deg2) to reduce possible source confusion. A prototype instrument has been tested in the polarized soft gamma-ray beams at Advanced Photon Source (ANL) and at Photon Factory (KEK). On the results, the polarization dependence of EGS4 has been validated and that of Geant4 has been corrected.
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