| 1. |
- 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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| 2. |
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| 3. |
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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
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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. |
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| 7. |
- Ablikim, M., et al.
(författare)
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Observation of χc2→η′η′ and χc0,2→ηη′
- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:11
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 448.1×106 ψ(3686) events collected with the BESIII detector in 2009 and 2012, we study the decays χc0,2→η′η′ and ηη′. The decays χc2→η′η′, χc0→ηη′ and χc2→ηη′ are observed for the first time with statistical significances of 9.6σ, 13.4σ and 7.5σ, respectively. The branching fractions are determined to be B(χc0→η′η′)=(2.19±0.03±0.14)×10−3, B(χc2→η′η′)=(4.76±0.56±0.38)×10−5, B(χc0→ηη′)=(8.92±0.84±0.65)×10−5 and B(χc2→ηη′)=(2.27±0.43±0.25)×10−5, where the first uncertainties are statistical and the second are systematic. The precision for the measurement of B(χc0→η′η′) is significantly improved compared to previous measurements. Based on the measured branching fractions, the role played by the doubly and singly Okubo-Zweig-Iizuka disconnected transition amplitudes for χc0,2 decays into pseudoscalar meson pairs can be clarified.
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| 8. |
- Ablikim, M., et al.
(författare)
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Improved measurements of two-photon widths of the chi(cJ) states and helicity analysis for chi(c2) -> gamma gamma
- 2017
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 96:9
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Tidskriftsartikel (refereegranskat)abstract
- Based on 448.1 x 10(6) Psi(3686) events collected with the BESIII detector, the decays Psi(3686) -> gamma chi(cJ), chi(cJ) -> gamma gamma(J = 0, 1, 2) are studied. The decay branching fractions of chi(c0,2) -> gamma gamma are measured to be B(chi(c0) -> gamma gamma) = (1.93 +/- 0.08 +/- 0.05 +/- 0.05) x 10(-4) and B(chi(c2) -> gamma gamma) = (3.10 +/- 0.09 +/- 0.07 +/- 0.11) x 10(-4) which correspond to two-photon decay widths of Gamma(gamma gamma)(chi(c0)) = 2.03 +/- 0.08 +/- 0.06 +/- 0.13 keV and Gamma(gamma gamma)(chi(c2)) = 0.60 +/- 0.02 +/- 0.01 +/- 0.04 keV with a ratio of R = Gamma(gamma gamma)(chi(c2))/Gamma(gamma gamma)(chi(c0)) = 0.295 +/- 0.014 +/- 0.007 +/- 0.027, where the uncertainties are statistical, systematic and associated with the uncertainties of B(Psi(3686) -> gamma chi(c0,2)) and the total widths Gamma(chi(c0,2)), respectively. For the forbidden decay of chi(c1) -> gamma gamma, no signal is observed, and an upper limit on the two-photon width is obtained to be Gamma(gamma gamma)(chi(c1)) < 5.3 eV at the 90% confidence level. The ratio of the two-photon widths between helicity-zero and helicity-two components in the decay chi(c2) -> gamma gamma is also measured to be f(0/2) = Gamma(lambda=0)(gamma gamma) (chi(c2))/Gamma(lambda=2)(gamma gamma) (chi(c2)) = (0.0 +/- 0.6 +/- 1.2) x 10(-2), where the uncertainties are statistical and systematic, respectively.
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| 9. |
- Ablikim, M., et al.
(författare)
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Observation of J/psi -> gamma eta pi(0)
- 2016
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Ingår i: PHYSICAL REVIEW D. - 2470-0010. ; 94:7
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Tidskriftsartikel (refereegranskat)abstract
- We present the first study of the process J/psi -> gamma eta pi(0) using (223.7 +/- 1.4) x 10(6) J/psi events accumulated with the BESIII detector at the BEPCII facility. The branching fraction for J/psi -> gamma eta pi(0) is measured to be B(J/psi -> gamma eta pi(0)) = (2.14 +/- 0.18(stat) +/- 0.25(syst)) x 10(-5). With a Bayesian approach, the upper limits of the branching fractions B(J/psi -> gamma a(0)(980), a(0)(980) -> eta pi(0)) and B(J/psi -> gamma a(2)(1320), a(2)(1320) -> eta pi(0)) are determined to be 2.5 x 10(-6) and 6.6 x 10(-6) at the 95% confidence level, respectively. All of these measurements are given for the first time.
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| 10. |
- Adare, A., et al.
(författare)
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Measurement of K-S(0) and K*(0) in p plus p, d plus Au, and Cu plus Cu collisions at root s(NN)=200 GeV
- 2014
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:5
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at the Relativistic Heavy Ion Collider has performed a systematic study of K-S(0) and K*(0) meson production at midrapidity in p + p, d + Au, and Cu + Cu collisions at root s(NN) = 200 GeV. The K-S(0) and K*(0) mesons are reconstructed via their K-S(0) -> pi(0)(-> gamma gamma) pi(0)(-> gamma gamma) and K*(0) -> K-+/-pi(-/+) decay modes, respectively. The measured transverse-momentum spectra are used to determine the nuclear modification factor of K-S(0) and K*(0) mesons in d + Au and Cu + Cu collisions at different centralities. In the d + Au collisions, the nuclear modification factor of K-S(0) and K*(0) mesons is almost constant as a function of transverse momentum and is consistent with unity, showing that cold-nuclear-matter effects do not play a significant role in the measured kinematic range. In Cu + Cu collisions, within the uncertainties no nuclear modification is registered in peripheral collisions. In central collisions, both mesons show suppression relative to the expectations from the p + p yield scaled by the number of binary nucleon-nucleon collisions in the Cu + Cu system. In the p(T) range 2-5 GeV/c, the strange mesons (K-S(0), K*(0)) similarly to the phi meson with hidden strangeness, showan intermediate suppression between the more suppressed light quark mesons (pi(0)) and the nonsuppressed baryons (p, (p) over bar). At higher transverse momentum, p(T) > 5 GeV/c, production of all particles is similarly suppressed by a factor of approximate to 2.
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