| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Ramdas, S., et al.
(författare)
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A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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| 7. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 8. |
- Aghasyan, M., et al.
(författare)
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Light isovector resonances in pi(-) p -> pi(-) pi(-) pi(+)p at 190 GeV/c
- 2018
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 98:9
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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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| 9. |
- Aghasyan, M., et al.
(författare)
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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
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Ingår i: Physics Letters B. - : ELSEVIER SCIENCE BV. - 0370-2693 .- 1873-2445. ; 781, s. 464-472
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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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| 10. |
- Aghasyan, M., et al.
(författare)
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Transverse-momentum-dependent multiplicities of charged hadrons in muon-deuteron deep inelastic scattering
- 2018
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:3
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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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