7 research outputs found

    New insights into the genetic etiology of Alzheimer's disease and related dementias.

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    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

    New insights into the genetic etiology of Alzheimer's disease and related dementias

    Get PDF
    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

    New insights into the genetic etiology of Alzheimer's disease and related dementias

    No full text
    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022. The Author(s)

    New insights into the genetic etiology of Alzheimer’s disease and related dementias

    No full text
    Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. © 2022, The Author(s)

    CMS Physics Technical Design Report: Addendum on High Density QCD with Heavy Ions

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    This report presents the capabilities of the CMS experiment to explore the rich heavy-ion physics programme offered by the CERN Large Hadron Collider (LHC). The collisions of lead nuclei at energies sNN=5.5TeV\sqrt{s_{NN}}= 5.5\,{\rm TeV} , will probe quark and gluon matter at unprecedented values of energy density. The prime goal of this research is to study the fundamental theory of the strong interaction \u2014 Quantum Chromodynamics (QCD) \u2014 in extreme conditions of temperature, density and parton momentum fraction (low- x ). This report covers in detail the potential of CMS to carry out a series of representative Pb-Pb measurements. These include "bulk" observables, (charged hadron multiplicity, low p T inclusive hadron identified spectra and elliptic flow) which provide information on the collective properties of the system, as well as perturbative probes such as quarkonia, heavy-quarks, jets and high p T hadrons which yield "tomographic" information of the hottest and densest phases of the reaction

    Measurement of dijet azimuthal decorrelation in pp collisions at √s=8TeV

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    A measurement of the decorrelation of azimuthal angles between the two jets with the largest transverse momenta is presented for seven regions of leading jet transverse momentum up to 2.2TeV. The analysis is based on the proton-proton collision data collected with the CMS experiment at a centre-of-mass energy of 8TeV corresponding to an integrated luminosity of 19.7fb-1. The dijet azimuthal decorrelation is caused by the radiation of additional jets and probes the dynamics of multijet production. The results are compared to fixed-order predictions of perturbative quantum chromodynamics (QCD), and to simulations using Monte Carlo event generators that include parton showers, hadronization, and multiparton interactions. Event generators with only two outgoing high transverse momentum partons fail to describe the measurement, even when supplemented with next-to-leading-order QCD corrections and parton showers. Much better agreement is achieved when at least three outgoing partons are complemented through either next-to-leading-order predictions or parton showers. This observation emphasizes the need to improve predictions for multijet production. © 2016, CERN for the benefit of the CMS collaboration
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