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1.
  • Franceschini, Nora, et al. (författare)
  • GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
  • 2018
  • Ingår i: Nature Communications. - 20411723 (ISSN). ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
2.
  • Pulit, S. L., et al. (författare)
  • Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
  • 2018
  • Ingår i: Neurology-Genetics. - 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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3.
  • Abe, K., et al. (författare)
  • J-PARC Neutrino Beamline Upgrade Technical Design Report
  • 2019
  • Rapport (refereegranskat)abstract
    • <p>In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×10<sup>22</sup> protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.</p>
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7.
  • Aggarwal, M. M., et al. (författare)
  • Photon and eta production in p plus Pb and p plus C collisions at root(NN)-N-S=17.4 GeV
  • 2013
  • Ingår i: Nuclear Physics, Section A. - Elsevier. - 0375-9474. ; 898, s. 14-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements of direct photon production in p + Pb and p + C collisions at root(NN)-N-s = 17.4 GeV are presented. Upper limits on the direct photon yield as a function of p(T) are derived and compared to the results for Pb + Pb collisions at root(NN)-N-s = 17.3 GeV. The production of the eta meson, which is an important input to the direct photon signal extraction, has been determined in the eta -> 2 gamma channel for p + C collisions at root(NN)-N-s = 17.4 GeV. (c) 2012 Elsevier B.V. All rights reserved.
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8.
  • Aggarwal, M. M., et al. (författare)
  • Pion freeze-out time in Pb plus Pb collisions at 158 AGeV/c studied via pi(-)/pi(+) and K-/K+ ratios
  • 2006
  • Ingår i: European Physical Journal C. Particles and Fields. - Springer. - 1434-6044. ; 48:2, s. 343-352
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of the final state Coulomb interaction on particles produced in Pb + Pb collisions at 158AGeV/c has been investigated in the WA98 experiment through the study of the pi(-)/pi(+) and K-/K+ ratios measured as a function of T-m- (m)0. While the ratio for kaons shows no significant T-m dependence, the pi(-)/pi(+) ratio is enhanced at small T-m - (m)0 values with an enhancement that increases with centrality. A silicon pad detector located near the target is used to estimate the contribution of hyperon decays to the pi(-)/pi(+) ratio. The comparison of results with predictions of the RQMD model in which the Coulomb interaction has been incorporated allows to place constraints on the time of the pion freeze-out.
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9.
  • Aggarwal, M. M., et al. (författare)
  • Suppression of high-p(T) neutral pion production in central Pb+Pb collisions at root s(NN)=17.3 GeV relative to p+C and p+Pb collisions
  • 2008
  • Ingår i: Physical Review Letters. - American Physical Society. - 1079-7114. ; 100:24
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutral pion transverse momentum spectra were measured in p+C and p+Pb collisions at root s(NN) = 17.4 GeV at midrapidity (2.3 less than or similar to eta(lab)less than or similar to 3.0) over the range 0.7 less than or similar to p(T)less than or similar to 3.5 GeV/c. The spectra are compared to pi(0) spectra measured in Pb+Pb collisions at root s(NN) = 17.3 GeV in the same experiment. For a wide range of Pb+Pb centralities (N-part less than or similar to 300), the yield of pi(0)'s with p(T)greater than or similar to 2 GeV/c is larger than or consistent with the p+C or p+Pb yields scaled with the number of nucleon-nucleon collisions (N-coll), while for central Pb+Pb collisions with N-part greater than or similar to 350, the pi(0) yield is suppressed.
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10.
  • Deloukas, Panos, et al. (författare)
  • Large-scale association analysis identifies new risk loci for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 45:1, s. 25-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
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