Displaying publications 1 - 20 of 71 in total

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  1. Fulltext A search for new phenomena in pp collisions at [Formula: see text] in final states with missing transverse momentum and at least one jet using the [Formula: see text] variable
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2017;77(5):294.
    PMID: 28579921 DOI: 10.1140/epjc/s10052-017-4787-8
    A search for new phenomena is performed in final states containing one or more jets and an imbalance in transverse momentum in pp collisions at a centre-of-mass energy of 13[Formula: see text]. The analysed data sample, recorded with the CMS detector at the CERN LHC, corresponds to an integrated luminosity of 2.3[Formula: see text]. Several kinematic variables are employed to suppress the dominant background, multijet production, as well as to discriminate between other standard model and new physics processes. The search provides sensitivity to a broad range of new-physics models that yield a stable weakly interacting massive particle. The number of observed candidate events is found to agree with the expected contributions from standard model processes, and the result is interpreted in the mass parameter space of fourteen simplified supersymmetric models that assume the pair production of gluinos or squarks and a range of decay modes. For models that assume gluino pair production, masses up to 1575 and 975[Formula: see text] are excluded for gluinos and neutralinos, respectively. For models involving the pair production of top squarks and compressed mass spectra, top squark masses up to 400[Formula: see text] are excluded.
  2. Fulltext Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
    Schumacher FR, Al Olama AA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ, et al.
    Nat Genet, 2018 07;50(7):928-936.
    PMID: 29892016 DOI: 10.1038/s41588-018-0142-8
    Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.
  3. Author Correction: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
    Schumacher FR, Olama AAA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ, et al.
    Nat Genet, 2019 02;51(2):363.
    PMID: 30622367 DOI: 10.1038/s41588-018-0330-6
    In the version of this article initially published, the name of author Manuela Gago-Dominguez was misspelled as Manuela Gago Dominguez. The error has been corrected in the HTML and PDF version of the article.
  4. Fulltext Author Correction: Germline variation at 8q24 and prostate cancer risk in men of European ancestry
    Matejcic M, Saunders EJ, Dadaev T, Brook MN, Wang K, Sheng X, et al.
    Nat Commun, 2019 01 17;10(1):382.
    PMID: 30655571 DOI: 10.1038/s41467-019-08293-z
    The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.
  5. Fulltext Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
    Wang A, Shen J, Rodriguez AA, Saunders EJ, Chen F, Janivara R, et al.
    Nat Genet, 2023 Dec;55(12):2065-2074.
    PMID: 37945903 DOI: 10.1038/s41588-023-01534-4
    The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
  6. Fulltext Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
    Adams CD, Richmond R, Ferreira DLS, Spiller W, Tan V, Zheng J, et al.
    Cancer Epidemiol Biomarkers Prev, 2019 Jan;28(1):208-216.
    PMID: 30352818 DOI: 10.1158/1055-9965.EPI-18-0079
    BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).

    METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

    RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.

    CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.

    IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

  7. Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at [Formula: see text][Formula: see text]
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2015 06 26;75(6):288.
    PMID: 26146483
    The inclusive jet cross section for proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] was measured by the CMS Collaboration at the LHC with data corresponding to an integrated luminosity of 5.0[Formula: see text]. The measurement covers a phase space up to 2[Formula: see text] in jet transverse momentum and 2.5 in absolute jet rapidity. The statistical precision of these data leads to stringent constraints on the parton distribution functions of the proton. The data provide important input for the gluon density at high fractions of the proton momentum and for the strong coupling constant at large energy scales. Using predictions from perturbative quantum chromodynamics at next-to-leading order, complemented with electroweak corrections, the constraining power of these data is investigated and the strong coupling constant at the Z boson mass [Formula: see text] is determined to be [Formula: see text], which is in agreement with the world average.
  8. Constraints on the pMSSM, AMSB model and on other models from the search for long-lived charged particles in proton-proton collisions at [Formula: see text]
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2015 07 17;75(7):325.
    PMID: 26213486
    Stringent limits are set on the long-lived lepton-like sector of the phenomenological minimal supersymmetric standard model (pMSSM) and the anomaly-mediated supersymmetry breaking (AMSB) model. The limits are derived from the results presented in a recent search for long-lived charged particles in proton-proton collisions, based on data collected by the CMS detector at a centre-of-mass energy of 8 TeV at the Large Hadron Collider. In the pMSSM parameter sub-space considered, 95.9 % of the points predicting charginos with a lifetime of at least 10 ns are excluded. These constraints on the pMSSM are the first obtained at the LHC. Charginos with a lifetime greater than 100 ns and masses up to about 800 GeV in the AMSB model are also excluded. The method described can also be used to set constraints on other models.
  9. Distributions of topological observables in inclusive three- and four-jet events in pp collisions at [Formula: see text][Formula: see text]
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.
    Eur Phys J C Part Fields, 2015 07 01;75(7):302.
    PMID: 26190937
    This paper presents distributions of topological observables in inclusive three- and four-jet events produced in pp collisions at a centre-of-mass energy of 7[Formula: see text] with a data sample collected by the CMS experiment corresponding to a luminosity of 5.1[Formula: see text]. The distributions are corrected for detector effects, and compared with several event generators based on two- and multi-parton matrix elements at leading order. Among the considered calculations, MadGraph interfaced with pythia6 displays the overall best agreement with data.
  10. Fulltext Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry
    Darst BF, Shen J, Madduri RK, Rodriguez AA, Xiao Y, Sheng X, et al.
    medRxiv, 2023 May 15.
    PMID: 37292833 DOI: 10.1101/2023.05.12.23289860
    Genome-wide polygenic risk scores (GW-PRS) have been reported to have better predictive ability than PRS based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer risk variants from multi-ancestry GWAS and fine-mapping studies (PRS 269 ). GW-PRS models were trained using a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls used to develop the multi-ancestry PRS 269 . Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California/Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI=0.635-0.677) in African and 0.844 (95% CI=0.840-0.848) in European ancestry men and corresponding prostate cancer OR of 1.83 (95% CI=1.67-2.00) and 2.19 (95% CI=2.14-2.25), respectively, for each SD unit increase in the GW-PRS. However, compared to the GW-PRS, in African and European ancestry men, the PRS 269 had larger or similar AUCs (AUC=0.679, 95% CI=0.659-0.700 and AUC=0.845, 95% CI=0.841-0.849, respectively) and comparable prostate cancer OR (OR=2.05, 95% CI=1.87-2.26 and OR=2.21, 95% CI=2.16-2.26, respectively). Findings were similar in the validation data. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the multi-ancestry PRS 269 constructed with fine-mapping.
  11. Fulltext Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry
    Darst BF, Shen J, Madduri RK, Rodriguez AA, Xiao Y, Sheng X, et al.
    Am J Hum Genet, 2023 Jul 06;110(7):1200-1206.
    PMID: 37311464 DOI: 10.1016/j.ajhg.2023.05.010
    Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635-0.677) in African and 0.844 (95% CI = 0.840-0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67-2.00) and 2.19 (95% CI = 2.14-2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659-0.700 and AUC = 0.845, 95% CI = 0.841-0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87-2.26 and OR = 2.21, 95% CI = 2.16-2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.
  12. Event generator tunes obtained from underlying event and multiparton scattering measurements
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016 03 17;76:155.
    PMID: 27471433
    New sets of parameters ("tunes") for the underlying-event (UE) modelling of the pythia8, pythia6 and herwig++ Monte Carlo event generators are constructed using different parton distribution functions. Combined fits to CMS UE proton-proton ([Formula: see text]) data at [Formula: see text] and to UE proton-antiproton ([Formula: see text]) data from the CDF experiment at lower [Formula: see text], are used to study the UE models and constrain their parameters, providing thereby improved predictions for proton-proton collisions at 13[Formula: see text]. In addition, it is investigated whether the values of the parameters obtained from fits to UE observables are consistent with the values determined from fitting observables sensitive to double-parton scattering processes. Finally, comparisons are presented of the UE tunes to "minimum bias" (MB) events, multijet, and Drell-Yan ([Formula: see text] lepton-antilepton+jets) observables at 7 and 8[Formula: see text], as well as predictions for MB and UE observables at 13[Formula: see text].
  13. Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC
    Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.
    Phys Rev Lett, 2024 Jan 12;132(2):021803.
    PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803
    The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140  fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
  14. Fulltext Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
    Dadaev T, Saunders EJ, Newcombe PJ, Anokian E, Leongamornlert DA, Brook MN, et al.
    Nat Commun, 2018 06 11;9(1):2256.
    PMID: 29892050 DOI: 10.1038/s41467-018-04109-8
    Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
  15. Fulltext Forward-backward asymmetry of Drell-Yan lepton pairs in pp collisions at [Formula: see text][Formula: see text]
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(6):325.
    PMID: 28280439 DOI: 10.1140/epjc/s10052-016-4156-z
    A measurement of the forward-backward asymmetry [Formula: see text] of oppositely charged lepton pairs ([Formula: see text] and [Formula: see text]) produced via [Formula: see text] boson exchange in pp collisions at [Formula: see text] [Formula: see text] is presented. The data sample corresponds to an integrated luminosity of 19.7[Formula: see text] collected with the CMS detector at the LHC. The measurement of [Formula: see text] is performed for dilepton masses between 40[Formula: see text] and 2[Formula: see text] and for dilepton rapidity up to 5. The [Formula: see text] measurements as a function of dilepton mass and rapidity are compared with the standard model predictions.
  16. Fulltext Germline variation at 8q24 and prostate cancer risk in men of European ancestry
    Matejcic M, Saunders EJ, Dadaev T, Brook MN, Wang K, Sheng X, et al.
    Nat Commun, 2018 Nov 05;9(1):4616.
    PMID: 30397198 DOI: 10.1038/s41467-018-06863-1
    Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p 
  17. Fulltext Measurement of Long-Range Near-Side Two-Particle Angular Correlations in pp Collisions at sqrt[s]=13  TeV
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Phys Rev Lett, 2016 Apr 29;116(17):172302.
    PMID: 27176516 DOI: 10.1103/PhysRevLett.116.172302
    Results on two-particle angular correlations for charged particles produced in pp collisions at a center-of-mass energy of 13 TeV are presented. The data were taken with the CMS detector at the LHC and correspond to an integrated luminosity of about 270  nb^{-1}. The correlations are studied over a broad range of pseudorapidity (|η|<2.4) and over the full azimuth (ϕ) as a function of charged particle multiplicity and transverse momentum (p_{T}). In high-multiplicity events, a long-range (|Δη|>2.0), near-side (Δϕ≈0) structure emerges in the two-particle Δη-Δϕ correlation functions. The magnitude of the correlation exhibits a pronounced maximum in the range 1.0
  18. Measurement of WZ and ZZ production in pp collisions at [Formula: see text] in final states with b-tagged jets
    CMS Collaboration, Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, et al.
    Eur Phys J C Part Fields, 2014 08 07;74(8):2973.
    PMID: 25814904
    Measurements are reported of the WZ and ZZ production cross sections in proton-proton collisions at [Formula: see text][Formula: see text] in final states where one Z boson decays to b-tagged jets. The other gauge boson, either W or Z, is detected through its leptonic decay (either [Formula: see text], [Formula: see text] or [Formula: see text], [Formula: see text], or [Formula: see text]). The results are based on data corresponding to an integrated luminosity of 18.9 fb[Formula: see text] collected with the CMS detector at the Large Hadron Collider. The measured cross sections, [Formula: see text] and [Formula: see text], are consistent with next-to-leading order quantum chromodynamics calculations.
  19. Fulltext Measurement of [Formula: see text] production with additional jet activity, including [Formula: see text] quark jets, in the dilepton decay channel using pp collisions at [Formula: see text]
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016;76(7):379.
    PMID: 28280447 DOI: 10.1140/epjc/s10052-016-4105-x
    Jet multiplicity distributions in top quark pair ([Formula: see text]) events are measured in pp collisions at a centre-of-mass energy of 8 TeV with the CMS detector at the LHC using a data set corresponding to an integrated luminosity of 19.7[Formula: see text]. The measurement is performed in the dilepton decay channels ([Formula: see text], [Formula: see text], and [Formula: see text]). The absolute and normalized differential cross sections for [Formula: see text] production are measured as a function of the jet multiplicity in the event for different jet transverse momentum thresholds and the kinematic properties of the leading additional jets. The differential [Formula: see text] and [Formula: see text] cross sections are presented for the first time as a function of the kinematic properties of the leading additional [Formula: see text] jets. Furthermore, the fraction of events without additional jets above a threshold is measured as a function of the transverse momenta of the leading additional jets and the scalar sum of the transverse momenta of all additional jets. The data are compared and found to be consistent with predictions from several perturbative quantum chromodynamics event generators and a next-to-leading order calculation.
  20. Measurement of differential cross sections for Higgs boson production in the diphoton decay channel in pp collisions at [Formula: see text]
    Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Asilar E, Bergauer T, et al.
    Eur Phys J C Part Fields, 2016 01 11;76:13.
    PMID: 26855607
    A measurement is presented of differential cross sections for Higgs boson (H) production in pp collisions at [Formula: see text][Formula: see text]. The analysis exploits the [Formula: see text] decay in data corresponding to an integrated luminosity of 19.7[Formula: see text] collected by the CMS experiment at the LHC. The cross section is measured as a function of the kinematic properties of the diphoton system and of the associated jets. Results corrected for detector effects are compared with predictions at next-to-leading order and next-to-next-to-leading order in perturbative quantum chromodynamics, as well as with predictions beyond the standard model. For isolated photons with pseudorapidities [Formula: see text], and with the photon of largest and next-to-largest transverse momentum ([Formula: see text]) divided by the diphoton mass [Formula: see text] satisfying the respective conditions of [Formula: see text] and [Formula: see text], the total fiducial cross section is [Formula: see text][Formula: see text].
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