| 1. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Mishra, A., et al.
(author)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Journal article (peer-reviewed)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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| 4. |
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| 5. |
- Winkler, TW, et al.
(author)
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Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals
- 2022
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 580-
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Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.
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| 7. |
- David, P., et al.
(author)
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Gaia Focused Product Release: Asteroid orbital solution : Properties and assessment
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 680
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Journal article (peer-reviewed)abstract
- Context. We report the exploitation of a sample of Solar System observations based on data from the third Gaia Data Release (Gaia DR3) of nearly 157 000 asteroids. It extends the epoch astrometric solution over the time coverage planned for the Gaia DR4, which is not expected before the end of 2025. This data set covers more than one full orbital period for the vast majority of these asteroids. The orbital solutions are derived from the Gaia data alone over a relatively short arc compared to the observation history of many of these asteroids.Aims. The work aims to produce orbital elements for a large set of asteroids based on 66 months of accurate astrometry provided by Gaia and to assess the accuracy of these orbital solutions with a comparison to the best available orbits derived from independent observations. A second validation is performed with accurate occultation timings.Methods. We processed the raw astrometric measurements of Gaia to obtain astrometric positions of moving objects with 1D sub-mas accuracy at the bright end. For each asteroid that we matched to the data, an orbit fitting was attempted in the form of the best fit of the initial conditions at the median epoch. The force model included Newtonian and relativistic accelerations to derive the observation equations, which were solved with a linear least-squares fit.Results. Orbits are provided in the form of state vectors in the International Celestial Reference Frame for 156 764 asteroids, including near-Earth objects, main-belt asteroids, and Trojans. For the asteroids with the best observations, the (formal) relative uncertainty σa/a is better than 10-10. Results are compared to orbits available from the Jet Propulsion Laboratory and MPC. Their orbits are based on much longer data arcs, but from positions of lower quality. The relative differences in semi-major axes have a mean of 5 × 10-10 and a scatter of 5 × 10-9
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| 9. |
- Krone-Martins, A., et al.
(author)
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Gaia Focused Product Release: A catalogue of sources around quasars to search for strongly lensed quasars
- 2024
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 685
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Journal article (peer-reviewed)abstract
- Context. Strongly lensed quasars are fundamental sources for cosmology. The Gaia space mission covers the entire sky with the unprecedented resolution of 0.18âà € ³ in the optical, making it an ideal instrument to search for gravitational lenses down to the limiting magnitude of 21. Nevertheless, the previous Gaia Data Releases are known to be incomplete for small angular separations such as those expected for most lenses.Aims. We present the Data Processing and Analysis Consortium GravLens pipeline, which was built to analyse all Gaia detections around quasars and to cluster them into sources, thus producing a catalogue of secondary sources around each quasar. We analysed the resulting catalogue to produce scores that indicate source configurations that are compatible with strongly lensed quasars.Methods. GravLens uses the DBSCAN unsupervised clustering algorithm to detect sources around quasars. The resulting catalogue of multiplets is then analysed with several methods to identify potential gravitational lenses. We developed and applied an outlier scoring method, a comparison between the average BP and RP spectra of the components, and we also used an extremely randomised tree algorithm. These methods produce scores to identify the most probable configurations and to establish a list of lens candidates.Results. We analysed the environment of 3 760 032 quasars. A total of 4 760 920 sources, including the quasars, were found within 6âà € ³ of the quasar positions. This list is given in the Gaia archive. In 87% of cases, the quasar remains a single source, and in 501 385 cases neighbouring sources were detected. We propose a list of 381 lensed candidates, of which we identified 49 as the most promising ones. Beyond these candidates, the associate tables in this Focused Product Release allow the entire community to explore the unique Gaia data for strong lensing studies further.
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