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| 3. |
- 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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| 4. |
- 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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| 5. |
- Adare, A., et al.
(författare)
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Measurements of Elliptic and Triangular Flow in High-Multiplicity He-3 + Au Collisions at root s(NN)=200 GeV
- 2015
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Ingår i: Physical Review Letters. - 1079-7114. ; 115:14
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Tidskriftsartikel (refereegranskat)abstract
- We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity He-3 + Au collisions at root s(NN) = 200 GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in He-3 + Au and in p + p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the He-3 + Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d + Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three He-3 nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.
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| 6. |
- Ablikim, M., et al.
(författare)
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Observation of ψ(3686)→n¯n and improved measurement of ψ(3686)→p¯p
- 2018
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 98:3
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Tidskriftsartikel (refereegranskat)abstract
- We observe the decay psi (3686) -> n (n) over bar for the first time and measure psi (3686) -> p (p) over bar with improved accuracy by using 1.07 x 10(8) psi (3686) events collected with the BESIII detector. The measured branching fractions are B(psi(3686) -> n (n) over bar) = (3.06 +/- 0.06 +/- 0.14) x 10(-4) and B(psi(3686) -> p (p) over bar) = (3.05 +/- 0.02 +/- 0.12) x 10(-4). Here, the first uncertainties are statistical, and the second ones are systematic. With the hypothesis that the polar angular distributions of the neutron and proton in the center-of-mass system obey 1 + alpha cos(2) theta, we determine the a parameters to be alpha(n (n) over bar) = 0.68 +/- 0.12 +/- 0.11 and alpha(p (p) over bar) = 1.03 +/- 0.06 +/- 0.03 for psi(3686) -> n (n) over bar and psi(3686) -> p (p) over bar, respectively.
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| 7. |
- Ablikim, M., et al.
(författare)
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Search for h(c) -> pi(+)pi(-) J/psi via psi(3686) -> pi(0)pi(+)pi(-) J/psi
- 2018
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Ingår i: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 97:5
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Tidskriftsartikel (refereegranskat)abstract
- Using a data sample of 448.1 x 10(6) psi(3686) events collected with the BESIII detector operating at the BEPCII, we perform search for the hadronic transition h(c)-> pi(+)pi(-) J/psi via psi (3686) -> pi(0)hc. No signals of the transition are observed, and the upper limit on the product branching fraction B(sigma(3686) -> pi(0)h(c))B(h(c) -> pi(+)pi(-) J/psi) at the 90% confidence level (C. L.) is determined to be 2.0 x 10(-6). This is the most stringent upper limit to date.
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| 8. |
- Ablikim, M., et al.
(författare)
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Study of two-photon decays of pseudoscalar mesons via J/Psi radiative decays
- 2018
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 97:7
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 4.48 x 10(8) Psi(3686) events collected with the BESIII detector at the BEPCII collider, we study the two-photon decays of the pseudoscalar mesons pi(0,) eta , eta' , eta(1405), eta(1475), eta(1760), and X(1835) in J/Psi radiative decays using Psi(3686) -> pi(+) pi(-) J/Psi events. The pi(0), eta, and eta' mesons are clearly observed in the two-photon mass spectra, and the branching fractions are determined to be B(J/Psi -> gamma pi(0) -> 3 gamma) = (3.57 +/- 0.12 +/- 0.16) x 10(-5), B(J/Psi -> gamma eta -> 3 gamma) = (4.42 +/- 0.04 +/- 0.18) x 10(-4), and B(J/Psi -> gamma eta' -> 2 gamma) = (1.26 +/- 0.02 +/- 0.05) x 10(-4), where the first error is statistical and the second is systematic. No clear signal for eta(1405), eta(1475), eta(1760) or X(1835) is observed in the two- photon mass spectra, and upper limits at the 90% confidence level on the product branching fractions are obtained.
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| 9. |
- Ablikim, M., et al.
(författare)
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Study of J/ψ and ψ(3686) decays to π+π−η′
- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:11
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Tidskriftsartikel (refereegranskat)abstract
- Using the data samples of 1.31×109 J/ψ events and 4.48×108 ψ(3686) events collected with the BESIII detector, partial wave analyses on the decays J/ψ and ψ(3686)→π+π−η′ are performed with a relativistic covariant tensor amplitude approach. The dominant contribution is found to be J/ψ and ψ(3686) decays to ρη′. In the J/ψ decay, the branching fraction B(J/ψ→ρη′) is determined to be (7.90±0.19(stat)±0.49(sys))×10−5. Two solutions are found in the ψ(3686) decay, and the corresponding branching fraction B(ψ(3686)→ρη′) is (1.02±0.11(stat)±0.24(sys))×10−5 for the case of destructive interference, and (5.69±1.28(stat)±2.36(sys))×10−6 for constructive interference. As a consequence, the ratios of branching fractions between ψ(3686) and J/ψ decays to ρη′ are calculated to be (12.9±1.4(stat)±3.1(sys))% and (7.2±1.6(stat)±3.0(sys))%, respectively. We also determine the inclusive branching fractions of J/ψ and ψ(3686) decays to π+π−η′ to be (1.36±0.02(stat)±0.08(sys))×10−4 and (1.51±0.14(stat)±0.23(sys))×10−5, respectively
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| 10. |
- Ablikim, M., et al.
(författare)
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Measurement of e(+)e(-) -> K(K)over-barJ/psi cross sections at center-of-mass energies from 4.189 to 4.600 GeV
- 2018
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 97:7
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the process e(+)e(-) -> K (K) over barJ/psi at center-of-mass energies from 4.189 to 4.600 GeV using 4.7 fb(-1) of data collected by the BESIII detector at the BEPCII collider. The Born cross sections for the reactions e(+)e(-) -> K(+)K(-)J/psi and K(S)(0)K(S)(0)J/psi are measured as a function of center-of-mass energy. The energy dependence of the cross section for e(+)e(-) -> K(+)K(-)J/psi is shown to differ from that for pi(+)pi(-)J/psi in the region around the Y(4260). In addition, there is evidence for a structure around 4.5 GeV in the e(+)e(-) -> K(+)K(-)J/psi cross section that is not present in pi(+)pi(-)J/psi.
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