365 research outputs found

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

    Get PDF
    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    Finishing the euchromatic sequence of the human genome

    Get PDF
    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Genomic reconstruction of the SARS-CoV-2 epidemic in England

    Get PDF
    AbstractThe evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.</jats:p

    World Congress Integrative Medicine & Health 2017: part two

    No full text

    Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s\sqrt{s} = 5.02 TeV

    No full text
    International audienceThe inclusive jet cross section is measured as a function of jet transverse momentum pTp_\mathrm{T} and rapidity yy. The measurement is performed using proton-proton collision data at s\sqrt{s} = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb1^{-1}. The jets are reconstructed with the anti-kTk_\mathrm{T} algorithm using a distance parameter of RR = 0.4, within the rapidity interval y\lvert y\rvert<\lt 2, and across the kinematic range 0.06 <\ltpTp_\mathrm{T}<\lt 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling αS\alpha_\mathrm{S}

    First evidence for off-shell production of the Higgs boson and measurement of its width

    No full text
    The first evidence for off-shell Higgs production is reported in the final state with two Z bosons decaying into either four charged leptons (muons or electrons), or two charged leptons and two neutrinos, and a measurement of the Higgs boson width is performed. Results are based on data from the CMS experiment at the LHC at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of up to 140 fb1^{-1}. The total rate of off-shell Higgs boson production beyond the Z boson pair production threshold, relative to its standard model expectation, is constrained to the interval [0.0061, 2.0] at 95% confidence level. The scenario with no off-shell production is excluded at 99.97% confidence level (3.6 standard deviations). The width of the Higgs boson is extracted as ΓH\Gamma_{\mathrm{H}} = 3.21.7+2.4_{-1.7}^{+2.4} MeV, in agreement with the standard model expectation of 4.1 MeV. The data are also used to set new constraints on anomalous Higgs boson couplings to W and Z boson pairs

    Measurement of inclusive and differential cross sections for single top quark production in association with a W boson in proton-proton collisions at s \sqrt{s} = 13 TeV

    No full text
    International audienceMeasurements of the inclusive and normalised differential cross sections are presented for the production of single top quarks in association with a W boson in proton-proton collisions at a centre-of-mass energy of 13 TeV. The data used were recorded with the CMS detector at the LHC during 2016–2018, and correspond to an integrated luminosity of 138 fb1^{−1}. Events containing one electron and one muon in the final state are analysed. For the inclusive measurement, a multivariate discriminant, exploiting the kinematic properties of the events is used to separate the signal from the dominant tt \textrm{t}\overline{\textrm{t}} background. A cross section of 79.2±0.9(stat)8.0+7.7(syst)±1.2(lumi) 79.2\pm 0.9{\left(\textrm{stat}\right)}_{-8.0}^{+7.7}\left(\textrm{syst}\right)\pm 1.2\left(\textrm{lumi}\right) pb is obtained, consistent with the predictions of the standard model. For the differential measurements, a fiducial region is defined according to the detector acceptance, and the requirement of exactly one jet coming from the fragmentation of a bottom quark. The resulting distributions are unfolded to particle level and agree with the predictions at next-to-leading order in perturbative quantum chromodynamics.[graphic not available: see fulltext

    Search for stealth supersymmetry in final states with two photons, jets, and low missing transverse momentum in proton-proton collisions at s\sqrt{s} = 13 TeV

    No full text
    International audienceThe results of a search for stealth supersymmetry in final states with two photons and jets, targeting a phase space region with low missing transverse momentum (pTmissp_\text{T}^\text{miss}), are reported. The study is based on a sample of proton-proton collisions at s\sqrt{s} =13 TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138 fb1^{-1}. As LHC results continue to constrain the parameter space of the minimal supersymmetric standard model, the low pTmissp_\text{T}^\text{miss} regime is increasingly valuable to explore. To estimate the backgrounds due to standard model processes in such events, we apply corrections derived from simulation to an estimate based on a control selection in data. The results are interpreted in the context of simplified stealth supersymmetry models with gluino and squark pair production. The observed data are consistent with the standard model predictions, and gluino (squark) masses of up to 2150 (1850) GeV are excluded at the 95% confidence level

    Search for nonresonant Higgs boson pair production in final state with two bottom quarks and two tau leptons in proton-proton collisions at <math altimg="si1.svg"><msqrt><mrow><mi>s</mi></mrow></msqrt><mo linebreak="goodbreak" linebreakstyle="after">=</mo><mn>13</mn><mtext> TeV</mtext></math>

    No full text
    International audienceA search for the nonresonant production of Higgs boson pairs (HH ) via gluon-gluon and vector boson fusion processes in final states with two bottom quarks and two tau leptons is presented. The search uses data from proton-proton collisions at a center-of-mass energy of s=13TeV recorded with the CMS detector at the LHC, corresponding to an integrated luminosity of 138fb−1. Events in which at least one tau lepton decays hadronically are considered and multiple machine learning techniques are used to identify and extract the signal. The data are found to be consistent, within uncertainties, with the standard model (SM) predictions. Upper limits on the HH production cross section are set to constrain the parameter space for anomalous Higgs boson couplings. The observed (expected) upper limit at 95% confidence level corresponds to 3.3 (5.2) times the SM prediction for the inclusive HH cross section and to 124 (154) times the SM prediction for the vector boson fusion HH cross section. At 95% confidence level, the Higgs field self-coupling is constrained to be within −1.7 and 8.7 times the SM expectation, and the coupling of two Higgs bosons to two vector bosons is constrained to be within −0.4 and 2.6 times the SM expectation
    corecore