| 1. |
- Adolph, C., et al.
(författare)
-
Azimuthal asymmetries of charged hadrons produced in high-energy muon scattering off longitudinally polarised deuterons
- 2018
-
Ingår i: European Physical Journal C. - : SPRINGER. - 1434-6044 .- 1434-6052. ; 78:11
-
Tidskriftsartikel (refereegranskat)abstract
- Single hadron azimuthal asymmetries of positive and negative hadrons produced in muon semi-inclusive deep inelastic scattering off longitudinally polarised deuterons are determined using the 2006 COMPASS data and also combined all deuteron COMPASS data. For each hadron charge, the dependence of the azimuthal asymmetry on the hadron azimuthal angle f is obtained by means of a fiveparameter fitting function that besides a f-independent term includes four modulations predicted by theory: sin f, sin 2f, sin 3f and cos f. The amplitudes of the five terms have been extracted, first, for the hadrons in the whole available kinematic region. In further fits, performed for hadrons from a restricted kinematic region, the f-dependence is determined as a function of one of three variables (Bjorken-x, fractional energy of virtual photon taken by the outgoing hadron and hadron transverse momentum), while disregarding the others. Except thef-independent term, all themodulation amplitudes are very small, and no clear kinematic dependence could be observed within experimental uncertainties.
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| 2. |
- Adolph, C., et al.
(författare)
-
First measurement of the Sivers asymmetry for gluons using SIDIS data
- 2017
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 772, s. 854-864
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Tidskriftsartikel (refereegranskat)abstract
- The Sivers function describes the correlation between the transverse spin of a nucleon and the transverse motion of its partons. For quarks, it was studied in previous measurements of the azimuthal asymmetry of hadrons produced in semi-inclusive deep inelastic scattering of leptons off transversely polarised nucleon targets, and it was found to be non-zero. In this letter the evaluation of the Sivers asymmetry for gluons is presented. The contribution of the photon-gluon fusion subprocess is enhanced by requiring two high transverse-momentum hadrons. The analysis method is based on a Monte Carlo simulation that includes three hard processes: photon-gluon fusion, QCD Compton scattering and the leading-order virtual-photon absorption process. The Sivers asymmetries of the three processes are simultaneously extracted using the LEPTO event generator and a neural network approach. The method is applied to samples of events containing at least two hadrons with large transverse momentum from the COMPASS data taken with a 160 GeV/c muon beam scattered off transversely polarised deuterons and protons. With a significance of about two standard deviations, a negative value is obtained for the gluon Sivers asymmetry. The result of a similar analysis for a Collins-like asymmetry for gluons is consistent with zero. (C) 2017 The Author(s). Published by Elsevier B.V.
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| 3. |
- Adolph, C., et al.
(författare)
-
Multiplicities of charged kaons from deep-inelastic muon scattering off an isoscalar target
- 2017
-
Ingår i: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 767, s. 133-141
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Tidskriftsartikel (refereegranskat)abstract
- Precise measurements of charged-kaon multiplicities in deep inelastic scattering were performed. The results are presented in three-dimensional bins of the Bjorken scaling variable x, the relative virtual-photon energy y, and the fraction z of the virtual-photon energy carried by the produced hadron. The data were obtained by the COMPASS Collaboration by scattering 160 GeV muons off an isoscalar (LiD)-Li-6 target. They cover the kinematic domain 1 (GeV/c)(2) < Q(2) < 60 (GeV/c)(2) in the photon virtuality, 0.004 < x < 0.4, 0.1 < y < 0.7, 0.20 < z < 0.85, and W > 5 GeV/c(2) in the invariant mass of the hadronic system. The results from the sum of the z-integrated K+ and K- multiplicities at high x point to a value of the non-strange quark fragmentation function larger than obtained by the earlier DSS fit.
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| 4. |
- Adolph, C., et al.
(författare)
-
Multiplicities of charged pions and charged hadrons from deep-inelastic scattering of muons off an isoscalar target
- 2017
-
Ingår i: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 764, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Multiplicities of charged pions and charged hadrons produced in deep-inelastic scattering were measured in three-dimensional bins of the Bjorken scaling variable x, the relative virtual-photon energy y and the relative hadron energy z. Data were obtained by the COMPASS Collaboration using a 160 GeV muon beam and an isoscalar target ((LiD)-Li-6). They cover the kinematic domain in the photon virtuality Q(2) > 1 (GeV/c) 2, 0.004 < x < 0.4, 0.2 < z < 0.85 and 0.1 < y < 0.7. In addition, a leading-order pQCD analysis was performed using the pion multiplicity results to extract quark fragmentation functions.
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| 5. |
- Adolph, C., et al.
(författare)
-
Sivers asymmetry extracted in SIDIS at the hard scales of the Drell-Yan process at COMPASS
- 2017
-
Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 770, s. 138-145
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Tidskriftsartikel (refereegranskat)abstract
- Eight proton transverse-spin-dependent azimuthal asymmetries are extracted in four regions of the photon virtuality Q(2) from the COMPASS 2010 semi-inclusive hadron measurements in deep inelastic muon nucleon scattering. These Q(2) regions correspond to the four regions of the di-muon mass root Q(2) used in the ongoing analyses of the COMPASS Drell-Yan measurements, which allows for a future direct comparison of the nucleon transverse-momentum-dependent parton distribution functions extracted from these two alternative measurements. In addition, for the azimuthal asymmetries induced by the Sivers transverse-momentum-dependent parton distribution function various two-dimensional kinematic dependences are presented. The integrated Sivers asymmetries are found to be positive with an accutacy that appears to be sufficient to test the sign change of the Sivers function predicted by Quantum Chromodynamics.
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| 6. |
- Adolph, C., et al.
(författare)
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Interplay among transversity induced asymmetries in hadron leptoproduction
- 2016
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 753, s. 406-411
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Tidskriftsartikel (refereegranskat)abstract
- In the fragmentation of a transversely polarized quark several left-right asymmetries are possible for the hadrons in the jet. When only one unpolarized hadron is selected, it exhibits an azimuthal modulation known as the Collins effect. When a pair of oppositely charged hadrons is observed, three asymmetries can be considered, a di-hadron asymmetry and two single hadron asymmetries. In lepton deep inelastic scattering on transversely polarized nucleons all these asymmetries are coupled with the transversity distribution. From the high statistics COMPASS data on oppositely charged hadron-pair production we have investigated for the first time the dependence of these three asymmetries on the difference of the azimuthal angles of the two hadrons. The similarity of transversity induced single and di-hadron asymmetries is discussed. A new analysis of the data allows quantitative relationships to be established among them, providing for the first time strong experimental indication that the underlying fragmentation mechanisms are all driven by a common physical process.
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| 7. |
- Adolph, C., et al.
(författare)
-
Resonance production and pi pi S-wave in pi(-) + p -> pi(-) pi(-) pi(+) + p(recoil) at 190 GeV/c
- 2017
-
Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 95:3
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Tidskriftsartikel (refereegranskat)abstract
- The COMPASS collaboration has collected the currently largest data set on diffractively produced pi(-) pi(-) pi(+) final states using a negative pion beam of 190 GeV/c momentum impinging on a stationary proton target. This data set allows for a systematic partial-wave analysis in 100 bins of three-pion mass, 0.5 < m(3 pi) < 2.5 GeV/c(2), and in 11 bins of the reduced four-momentum transfer squared, 0.1 < t' < 1.0 (GeV/c)(2). This two-dimensional analysis offers sensitivity to genuine one-step resonance production, i.e. the production of a state followed by its decay, as well as to more complex dynamical effects in nonresonant 3 pi production. In this paper, we present detailed studies on selected 3p partial waves with J(PC) = 0(-+) ,1(++) ,2(-+) ,2(++) ,and 4(++). In these waves, we observe the well-known groundstate mesons as well as a new narrow axial-vector meson a(1)(1420) decaying into f(0) (980)pi. In addition, we present the results of a novel method to extract the amplitude of the pi(-)pi(+) subsystem with I(G)J(PC) = 0(+)0(++) in various partial waves from the pi(-)pi(-)pi(+) data. Evidence is found for correlation of the f (0)(980) and f(0)(1500) appearing as intermediate pi(-)pi(+) isobars in the decay of the known pi(1800) and pi(2)(1880).
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| 8. |
- Adolph, C., et al.
(författare)
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The spin structure function g(1)(p) of the proton and a test of the Bjorken sum rule
- 2016
-
Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 753, s. 18-28
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Tidskriftsartikel (refereegranskat)abstract
- New results for the double spin asymmetry A(1)(p) and the proton longitudinal spin structure function g(1)(p) are presented. They were obtained by the COMPASS Collaboration using polarised 200 GeV muons scattered off a longitudinally polarised NH3 target. The data were collected in 2011 and complement those recorded in 2007 at 160 GeV, in particular at lower values of x. They improve the statistical precision of g(1)(p)(x) by about a factor of two in the region x less than or similar to 0.02. A next-to-leading order QCD fit to the g(1) world data is performed. It leads to a new determination of the quark spin contribution to the nucleon spin, Delta Sigma, ranging from 0.26 to 0.36, and to a re-evaluation of the first moment of g(1)(p). The uncertainty of Delta Sigma is mostly due to the large uncertainty in the present determinations of the gluon helicity distribution. A new evaluation of the Bjorken sum rule based on the COMPASS results for the non-singlet structure function g(1)(NS) (x, Q(2)) yields as ratio of the axial and vector coupling constants vertical bar gA/gV vertical bar = 1.22 +/- 0.05 (stat.) +/- 0.10 (syst.), which validates the sum rule to an accuracy of about 9%.
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| 9. |
- Adolphi, C., et al.
(författare)
-
Exclusive omega meson muoproduction on transversely polarised protons
- 2017
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Ingår i: Nuclear Physics B. - : ELSEVIER SCIENCE BV. - 0550-3213 .- 1873-1562. ; 915, s. 454-475
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Tidskriftsartikel (refereegranskat)abstract
- Exclusive production of omega mesons was studied at the COMPASS experiment by scattering 160GeV/c muons off transversely polarised protons. Five single-spin and three double-spin azimuthal asymmetries were measured in the range of photon virtuality 1(GeV/c)(2) < Q(2) < 10(GeV/c)(2), Bjorken scaling variable 0.003 < xBj < 0.3 and transverse momentum squared of the omega meson 0.05(GeV/c)(2) < p(T)(2) < 0.5(GeV/c)(2). The measured asymmetries are sensitive to the nucleon helicity-flip Generalised Parton Distributions (GPD) Et hat are related to the orbital angular momentum of quarks, the chiral-odd GPDs H-T that are related to the transversity Parton Distribution Functions, and the sign of the pi omega transition form factor. The results are compared to recent calculations of a GPD-based model.
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| 10. |
- Aghasyan, M., et al.
(författare)
-
First Measurement of Transverse-Spin-Dependent Azimuthal Asymmetries in the Drell-Yan Process
- 2017
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 119:11
-
Tidskriftsartikel (refereegranskat)abstract
- The first measurement of transverse-spin-dependent azimuthal asymmetries in the pion-induced Drell-Yan (DY) process is reported. We use the CERN SPS 190 GeV/c pi(-) beam and a transversely polarized ammonia target. Three azimuthal asymmetries giving access to different transverse-momentum-dependent (TMD) parton distribution functions (PDFs) are extracted using dimuon events with invariant mass between 4.3 GeV/c(2) and 8.5 GeV/c(2). Within the experimental uncertainties, the observed sign of the Sivers asymmetry is found to be consistent with the fundamental prediction of quantum chromodynamics (QCD) that the Sivers TMD PDFs extracted from DY have a sign opposite to the one extracted from semi-inclusive deep-inelastic scattering (SIDIS) data. We present two other asymmetries originating from the pion Boer-Mulders TMD PDFs convoluted with either the nucleon transversity or pretzelosity TMD PDFs. A recent COMPASS SIDIS measurement was obtained at a hard scale comparable to that of these DY results. This opens the way for possible tests of fundamental QCD universality predictions.
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| 11. |
- Aghasyan, M., et al.
(författare)
-
Longitudinal double-spin asymmetry A(1)(p) and spin-dependent structure function g(1)(p) of the proton at small values of x and Q(2)
- 2018
-
Ingår i: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 781, s. 464-472
-
Tidskriftsartikel (refereegranskat)abstract
- We present a precise measurement of the proton longitudinal double-spin asymmetry A(1)(p) and the proton spin-dependent structure function g(1)(P) at photon virtualities 0.006 (GeV/c)(2) < Q(2) < 1 (GeV/c)(2) in the Bjorken x range of 4 x 10(-5) < x < 4 x 10(-2). The results are based on data collected by the COMPASS Collaboration at CERN using muon beam energies of 160 GeV and 200 GeV. The statistical precision is more than tenfold better than that of the previous measurement in this region. In the whole range of x, the measured values of A(1)(p) and g(1)(P) are found to be positive. It is for the first time that spin effects are found at such low values of x.
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| 12. |
- Aghasyan, M., et al.
(författare)
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Search for muoproduction of X(3872) at COMPASS and indication of a new state (X)over-tilde(3872)
- 2018
-
Ingår i: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 783, s. 334-340
-
Tidskriftsartikel (refereegranskat)abstract
- We have searched for exclusive production of exotic charmonia in the reaction mu N+ -> mu(+)(J/psi pi(+)pi(-))pi N-+/-' using COMPASS data collected with incoming muons of 160 GeV/c and 200 GeV/c momentum. In the J/psi pi(vertical bar)pi mass distribution we observe a signal with a statistical significance of 4.1 sigma. Its mass and width are consistent with those of the X(3872). The shape of the pi(+)pi(-) mass distribution from the observed decay into J/psi pi(+)pi(-) shows disagreement with previous observations for X(3872). The observed signal may be interpreted as a possible evidence of a new charmonium state. It could be associated with a neutral partner of X(3872) with C=-1 predicted by a tetraquark model. The product of cross section and branching fraction of the decay of the observed state into J/psi pi(+)pi(-) is determined to be 71 +/- 28(stat)+/- 39(syst) pb.
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| 13. |
- Aghasyan, M., et al.
(författare)
-
Transverse-momentum-dependent multiplicities of charged hadrons in muon-deuteron deep inelastic scattering
- 2018
-
Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:3
-
Tidskriftsartikel (refereegranskat)abstract
- A semi-inclusive measurement of charged hadron multiplicities in deep inelastic muon scattering off an isoscalar target was performed using data collected by the COMPASS Collaboration at CERN. The following kinematic domain is covered by the data: photon virtuality Q(2) > 1 (GeV/c)(2), invariant mass of the hadronic system W > 5 (GeV/c)(2), Bjorken scaling variable in the range 0.003 < x < 0.4, fraction of the virtual photon energy carried by the hadron in the range 0.2 < z < 0.8, and square of the hadron transverse momentum with respect to the virtual photon direction in the range 0.02 (GeV/c)(2) < P-hT(2) < 3 (GeV/c)(2). The multiplicities are presented as a function of P-hT(2) in three-dimensional bins of x, Q(2), z and compared to previous semi-inclusive measurements. We explore the small-P-hT(2) region, i.e. P-hT(2) < 1 (GeV/c)(2), where hadron transverse momenta are expected to arise from nonperturbative effects, and also the domain of larger P-hT(2), where contributions from higher-order perturbative QCD are expected to dominate. The multiplicities are fitted using a single-exponential function at small P-hT(2) to study the dependence of the average transverse momentum < P-hT(2)> on x, Q(2) and z. The power-law behavior of the multiplicities at large P-hT(2) is investigated using various functional forms. The fits describe the data reasonably well over the full measured range.
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| 14. |
- Jackura, A., et al.
(författare)
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New analysis of eta pi tensor resonances measured at the COMPASS experiment
- 2018
-
Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 779, s. 464-472
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Tidskriftsartikel (refereegranskat)abstract
- We present a new amplitude analysis of the eta pi D-wave in the reaction pi(-) p -> eta pi(-) p measured by COMPASS. Employing an analytical model based on the principles of the relativistic S-matrix, we find two resonances that can be identified with the a(2)(1320) and the excited a(2)(1700), and perform a comprehensive analysis of their pole positions. For the mass and width of the a(2) we find M = (1307 +/- 1 6) MeV and Gamma=(112 +/- 1 +/- 8) MeV, and for the excited state a(2)' we obtain M = (1720 +/- 10 +/- 60) MeV and Gamma = (280 +/- 10 +/- 70) MeV, respectively.
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| 15. |
- Aghasyan, M., et al.
(författare)
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Light isovector resonances in pi(-) p -> pi(-) pi(-) pi(+)p at 190 GeV/c
- 2018
-
Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 98:9
-
Tidskriftsartikel (refereegranskat)abstract
- We have performed the most comprehensive resonance-model fit of pi(-)pi(-)pi(+) states using the results of our previously published partial-wave analysis (PWA) of a large data set of diffractive-dissociation events from the reaction pi(-) + p -> pi(-)pi(-)pi(+) +p(recoil) with a 190 GeV/c pion beam. The PWA results, which were obtained in 100 bins of three-pion mass, 0.5 < m(3 pi) < 2.5 GeV/c(2), and simultaneously in 11 bins of the reduced four-momentum transfer squared, 0.1 < t'< 1.0 (GeV/c)(2), are subjected to a resonance-model fit using Breit-Wigner amplitudes to simultaneously describe a subset of 14 selected waves using 11 isovector light-meson states with J(PC) = 0(-+), 1(++), 2(++), 2(-+), 4(++), and spin-exotic 1(-+) quantum numbers. The model contains the well-known resonances pi(1800), a(1)(1260), a(2)(1320), pi(2)(1670), pi(2)(1880), and a(4) (2040). In addition, it includes the disputed pi(1)(1600), the excited states a(1)(1640), a2(1700), and pi(2) (2005), as well as the resonancelike a(1)(1420). We measure the resonance parameters mass and width of these objects by combining the information from the PWA results obtained in the 11 t' bins. We extract the relative branching fractions of the rho(770)pi and f(2)(1270)pi decays of a(2)(1320) and a(4)(2040), where the former one is measured for the first time. In a novel approach, we extract the t' dependence of the intensity of the resonances and of their phases. The t' dependence of the intensities of most resonances differs distinctly from the t' dependence of the nonresonant components. For the first time, we determine the t' dependence of the phases of the production amplitudes and confirm that the production mechanism of the Pomeron exchange is common to all resonances. We have performed extensive systematic studies on the model dependence and correlations of the measured physical parameters.
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| 16. |
- Akhunzyanov, R., et al.
(författare)
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Transverse extension of partons in the proton probed in the sea-quark range by measuring the DVCS cross section
- 2019
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Ingår i: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 793, s. 188-194
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Tidskriftsartikel (refereegranskat)abstract
- We report on the first measurement of exclusive single-photon muoproduction on the proton by COMPASS using 160 GeV/c polarised mu(+) and mu(-) beams of the CERN SPS impinging on a liquid hydrogen target. We determine the dependence of the average of the measured mu(+) and mu(-) cross sections for deeply virtual Compton scattering on the squared four-momentum transfer t from the initial to the final proton. The slope B of the t-dependence is fitted with a single exponential function, which yields B = (4.3 +/- 0.6(stat) (+0.1)(-0.3)vertical bar(sys)) (GeV/c)(-2). This result can be converted into a transverse extension of partons in the proton,root(r(perpendicular to)(2)) = (0.58 +/- 0.04(stat) (+0.01)(-0.02)vertical bar(sys) +/- 0.04(model)) fm. For this measurement, the average virtuality of the photon mediating the interaction is < Q(2)> = 1.8 (GeV/c)(2) and the average value of the Bjorken variable is < X-Bj > = 0.056.
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| 17. |
- Chasman, Daniel I., et al.
(författare)
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Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343
-
Tidskriftsartikel (refereegranskat)abstract
- In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
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| 18. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 19. |
- Pattaro, Cristian, et al.
(författare)
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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002584-
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genomewide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
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| 20. |
- Boeger, Carsten A., et al.
(författare)
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CUBN Is a Gene Locus for Albuminuria
- 2011
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:3, s. 555-570
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Tidskriftsartikel (refereegranskat)abstract
- Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
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| 21. |
- Köttgen, Anna, et al.
(författare)
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New loci associated with kidney function and chronic kidney disease
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:5, s. 376-384
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
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| 22. |
- Parsa, Afshin, et al.
(författare)
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Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- 2013
-
Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 24:12, s. 2105-2117
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Tidskriftsartikel (refereegranskat)abstract
- Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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| 23. |
- Kraemer, Bernhard K., et al.
(författare)
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Tacrolimus-Based, Steroid-Free Regimens in Renal Transplantation : 3-Year Follow-Up of the ATLAS Trial
- 2012
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 94:5, s. 492-498
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Tidskriftsartikel (refereegranskat)abstract
- Background. Long-term use of corticosteroids is associated with considerable morbidity, including cardiovascular and metabolic adverse effects. Methods. This study evaluated the long-term efficacy and safety of two steroid-free regimens compared with a triple immunosuppressive therapy in renal transplant recipients. This was a 3-year follow-up to a 6-month, open-label, randomized, multicenter study. Results. Data from 3 years were available for 421 (93.3%) of 451 patients in the original intent-to-treat population (143 tacrolimus/basiliximab [Tac/Bas], 139 tacrolimus/mycophenolate mofetil [Tac/MMF], and 139 tacrolimus/MMF/steroids [triple therapy]). In the time interval from 6 months to 3 years after transplantation, the incidence of biopsy-proven acute rejection was low and similar (Tac/Bas, 2.1%; Tac/MMF, 2.2%; triple therapy, 2.2%); Most rejection episodes occurred during the first 6 months of the study. Graft survival was high (Kaplan-Meier estimates: 92.7%, 92.5%, and 92.5%), as was patient survival (93.1%, 96.4%, and 97.0%). There were 10 graft losses (n=2, 4, and 4) and 12 patient deaths (n=5, 2, and 5). Renal function was well preserved throughout the study and similar between groups. There was a trend toward improved cardiovascular risk factors in the Tac/Bas group, including reduced total and low-density lipoprotein cholesterol and lower new-onset insulin use. There were no between-group differences in the incidence or type of adverse events. Conclusion. Higher rates of acute rejection early in treatment were seen with the steroid-free regimens, but this did not translate into poorer long-term outcomes, such as graft and patient survival and renal function. A trend for a more favorable cardiovascular risk profile was observed for steroid-free immunosuppression with Tac/Bas.
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| 24. |
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| 25. |
- Heinze, Karolin, et al.
(författare)
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Validated biomarker assays confirm ARID1A loss is confounded with MMR deficiency, CD8 TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.
- 2021
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Ingår i: The Journal of pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 256:4, s. 388-401
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Tidskriftsartikel (refereegranskat)abstract
- ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p<0.001), and presence of CD8+ TIL (p=0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOC we also observed an association between ARID1A loss-of-function mutation as a result of small indels (p=0.035, versus single nucleotide variants). In ENOC, the association between ARID1A loss, CD8+ TIL, and age, appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. This article is protected by copyright. All rights reserved.
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| 26. |
- Markmann, James F., et al.
(författare)
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Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of beta-Cell Replacement
- 2016
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 100:7, s. E25-E31
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Forskningsöversikt (refereegranskat)abstract
- The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation.
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| 27. |
- Zewinger, Stephen, et al.
(författare)
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Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease : a molecular and genetic association study
- 2017
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Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 5:7, s. 534-543
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.Findings: The median follow-up was 9.9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1.44, 95% CI 1.14-1.83) and the presence of either LPA SNP (1.88, 1.40-2.53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0.95, 0.81-1.11 and either LPA SNP 1.10, 0.92-1.31) or cardiovascular mortality (0.99, 0.81-1.2 and 1.13, 0.90-1.40, respectively) or in the validation studies.Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.
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