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2. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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- 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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- 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. |
- Panuzzo, P., et al.
(författare)
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Discovery of a dormant 33 solar-mass black hole in pre-release Gaia astrometry
- 2024
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 686
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Tidskriftsartikel (refereegranskat)abstract
- Context. Gravitational waves from black-hole (BH) merging events have revealed a population of extra-galactic BHs residing in short-period binaries with masses that are higher than expected based on most stellar evolution models-And also higher than known stellar-origin black holes in our Galaxy. It has been proposed that those high-mass BHs are the remnants of massive metal-poor stars.Aims. Gaia astrometry is expected to uncover many Galactic wide-binary systems containing dormant BHs, which may not have been detected before. The study of this population will provide new information on the BH-mass distribution in binaries and shed light on their formation mechanisms and progenitors.Methods. As part of the validation efforts in preparation for the fourth Gaia data release (DR4), we analysed the preliminary astrometric binary solutions, obtained by the Gaia Non-Single Star pipeline, to verify their significance and to minimise false-detection rates in high-mass-function orbital solutions.Results. The astrometric binary solution of one source, Gaia BH3, implies the presence of a 32.70a ±a 0.82aM- BH in a binary system with a period of 11.6 yr. Gaia radial velocities independently validate the astrometric orbit. Broad-band photometric and spectroscopic data show that the visible component is an old, very metal-poor giant of the Galactic halo, at a distance of 590 pc.Conclusions. The BH in the Gaia BH3 system is more massive than any other Galactic stellar-origin BH known thus far. The low metallicity of the star companion supports the scenario that metal-poor massive stars are progenitors of the high-mass BHs detected by gravitational-wave telescopes. The Galactic orbit of the system and its metallicity indicate that it might belong to the Sequoia halo substructure. Alternatively, and more plausibly, it could belong to the ED-2 stream, which likely originated from a globular cluster that had been disrupted by the Milky Way.
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6. |
- De Ridder, J., et al.
(författare)
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Gaia Data Release 3: Pulsations in main sequence OBAF-type stars
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Tidskriftsartikel (refereegranskat)abstract
- Context. The third Gaia data release provides photometric time series covering 34 months for about 10 million stars. For many of those stars, a characterisation in Fourier space and their variability classification are also provided. This paper focuses on intermediate- to high-mass (IHM) main sequence pulsators (M ≥ 1.3 M⊙) of spectral types O, B, A, or F, known as β Cep, slowly pulsating B (SPB), δ Sct, and γ Dor stars. These stars are often multi-periodic and display low amplitudes, making them challenging targets to analyse with sparse time series.Aims. We investigate the extent to which the sparse Gaia DR3 data can be used to detect OBAF-type pulsators and discriminate them from other types of variables. We aim to probe the empirical instability strips and compare them with theoretical predictions. The most populated variability class is that of the δ Sct variables. For these stars, we aim to confirm their empirical period-luminosity (PL) relation, and verify the relation between their oscillation amplitude and rotation.Methods. All datasets used in this analysis are part of the Gaia DR3 data release. The photometric time series were used to perform a Fourier analysis, while the global astrophysical parameters necessary for the empirical instability strips were taken from the Gaia DR3 gspphot tables, and the v sin i data were taken from the Gaia DR3 esphs tables. The δ Sct PL relation was derived using the same photometric parallax method as the one recently used to establish the PL relation for classical Cepheids using Gaia data.Results. We show that for nearby OBAF-type pulsators, the Gaia DR3 data are precise and accurate enough to pinpoint them in the Hertzsprung-Russell (HR) diagram. We find empirical instability strips covering broader regions than theoretically predicted. In particular, our study reveals the presence of fast rotating gravity-mode pulsators outside the strips, as well as the co-existence of rotationally modulated variables inside the strips as reported before in the literature. We derive an extensive period–luminosity relation for δ Sct stars and provide evidence that the relation features different regimes depending on the oscillation period. We demonstrate how stellar rotation attenuates the amplitude of the dominant oscillation mode of δ Sct stars.Conclusions. The Gaia DR3 time-series photometry already allows for the detection of the dominant (non-)radial oscillation mode in about 100 000 intermediate- and high-mass dwarfs across the entire sky. This detection capability will increase as the time series becomes longer, allowing the additional delivery of frequencies and amplitudes of secondary pulsation modes.
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7. |
- Drimmel, R., et al.
(författare)
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Gaia Data Release 3: Mapping the asymmetric disc of the Milky Way
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Tidskriftsartikel (refereegranskat)abstract
- Context. With the most recent Gaia data release, the number of sources with complete 6D phase space information (position and velocity) has increased to well over 33 million stars, while stellar astrophysical parameters are provided for more than 470 million sources, and more than 11 million variable stars are identified.Aims. Using the astrophysical parameters and variability classifications provided in Gaia DR3, we selected various stellar populations to explore and identify non-axisymmetric features in the disc of the Milky Way in configuration and velocity space.Methods. Using more about 580 000 sources identified as hot OB stars, together with 988 known open clusters younger than 100 Myr, we mapped the spiral structure associated with star formation 4−5 kpc from the Sun. We selected over 2800 Classical Cepheids younger than 200 Myr that show spiral features extending as far as 10 kpc from the Sun in the outer disc. We also identified more than 8.7 million sources on the red giant branch (RGB), of which 5.7 million have line-of-sight velocities. This later sample allows the velocity field of the Milky Way to be mapped as far as 8 kpc from the Sun, including the inner disc.Results. The spiral structure revealed by the young populations is consistent with recent results using Gaia EDR3 astrometry and source lists based on near-infrared photometry, showing the Local (Orion) Arm to be at least 8 kpc long, and an outer arm consistent with what is seen in HI surveys, which seems to be a continuation of the Perseus arm into the third quadrant. The subset of RGB stars with velocities clearly reveals the large-scale kinematic signature of the bar in the inner disc, as well as evidence of streaming motions in the outer disc that might be associated with spiral arms or bar resonances. A local comparison of the velocity field of the OB stars reveals similarities and differences with the RGB sample.Conclusions. This cursory study of Gaia DR3 data shows there is a rich bounty of kinematic information to be explored more deeply, which will undoubtedly lead us to a clearer understanding of the dynamical nature of the non-axisymmetric structures of the Milky Way.
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- Galluccio, L., et al.
(författare)
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Gaia Data Release 3: Reflectance spectra of Solar System small bodies
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Tidskriftsartikel (refereegranskat)abstract
- Context. The Gaia mission of the European Space Agency (ESA) has been routinely observing Solar System objects (SSOs) since the beginning of its operations in August 2014. The Gaia data release three (DR3) includes, for the first time, the mean reflectance spectra of a selected sample of 60 518 SSOs, primarily asteroids, observed between August 5, 2014, and May 28, 2017. Each reflectance spectrum was derived from measurements obtained by means of the Blue and Red photometers (BP/RP), which were binned in 16 discrete wavelength bands. For every spectrum, the DR3 also contains additional information about the data quality for each band.Aims. We describe the processing of the Gaia spectral data of SSOs, explaining both the criteria used to select the subset of asteroid spectra published in Gaia DR3, and the different steps of our internal validation procedures. In order to further assess the quality of Gaia SSO reflectance spectra, we carried out external validation against SSO reflectance spectra obtained from ground-based and space-borne telescopes and available in the literature; we present our validation approach.Methods. For each selected SSO, an epoch reflectance was computed by dividing the calibrated spectrum observed by the BP/RP at each transit on the focal plane by the mean spectrum of a solar analogue. The latter was obtained by averaging the Gaia spectral measurements of a selected sample of stars known to have very similar spectra to that of the Sun. Finally, a mean of the epoch reflectance spectra was calculated in 16 spectral bands for each SSO.Results. Gaia SSO reflectance spectra are in general agreement with those obtained from a ground-based spectroscopic campaign specifically designed to cover the same spectral interval as Gaia and mimic the illumination and observing geometry characterising Gaia SSO observations. In addition, the agreement between Gaia mean reflectance spectra and those available in the literature is good for bright SSOs, regardless of their taxonomic spectral class. We identify an increase in the spectral slope of S-type SSOs with increasing phase angle. Moreover, we show that the spectral slope increases and the depth of the 1 μm absorption band decreases for increasing ages of S-type asteroid families. The latter can be interpreted as proof of progressive ageing of S-type asteroid surfaces due to their exposure to space weathering effects.
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- Klioner, S. A., et al.
(författare)
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Gaia Early Data Release 3: The celestial reference frame (Gaia-CRF3)
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 667
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Tidskriftsartikel (refereegranskat)abstract
- Context. Gaia-CRF3 is the celestial reference frame for positions and proper motions in the third release of data from the Gaia mission, Gaia DR3 (and for the early third release, Gaia EDR3, which contains identical astrometric results). The reference frame is defined by the positions and proper motions at epoch 2016.0 for a specific set of extragalactic sources in the (E)DR3 catalogue.Aims. We describe the construction of Gaia-CRF3 and its properties in terms of the distributions in magnitude, colour, and astrometric quality.Methods. Compact extragalactic sources in Gaia DR3 were identified by positional cross-matching with 17 external catalogues of quasi-stellar objects (QSO) and active galactic nuclei (AGN), followed by astrometric filtering designed to remove stellar contaminants. Selecting a clean sample was favoured over including a higher number of extragalactic sources. For the final sample, the random and systematic errors in the proper motions are analysed, as well as the radio-optical offsets in position for sources in the third realisation of the International Celestial Reference Frame (ICRF3).Results. Gaia-CRF3 comprises about 1.6 million QSO-like sources, of which 1.2 million have five-parameter astrometric solutions in Gaia DR3 and 0.4 million have six-parameter solutions. The sources span the magnitude range G = 13-21 with a peak density at 20.6 mag, at which the typical positional uncertainty is about 1 mas. The proper motions show systematic errors on the level of 12 μas yr-1 on angular scales greater than 15 deg. For the 3142 optical counterparts of ICRF3 sources in the S/X frequency bands, the median offset from the radio positions is about 0.5 mas, but it exceeds 4 mas in either coordinate for 127 sources. We outline the future of Gaia-CRF in the next Gaia data releases. Appendices give further details on the external catalogues used, how to extract information about the Gaia-CRF3 sources, potential (Galactic) confusion sources, and the estimation of the spin and orientation of an astrometric solution.
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- Lindegren, L., et al.
(författare)
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Gaia Data Release 3: A golden sample of astrophysical parameters
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Tidskriftsartikel (refereegranskat)abstract
- Context. Gaia Data Release 3 (DR3) provides a wealth of new data products for the astronomical community to exploit, including astrophysical parameters for half a billion stars. In this work, we demonstrate the high quality of these data products and illustrate their use in different astrophysical contexts.Aims. We produce homogeneous samples of stars with high-quality astrophysical parameters by exploiting Gaia DR3, while focusing on many regimes across the Hertzsprung-Russell (HR) diagram; spectral types OBA, FGKM, and ultracool dwarfs (UCDs). We also focus on specific subsamples of particular interest to the community: solar analogues, carbon stars, and the Gaia spectrophotometric standard stars (SPSS).Methods. We query the astrophysical parameter tables along with other tables in Gaia DR3 to derive the samples of the stars of interest. We validate our results using the Gaia catalogue itself and by comparison with external data.Results. We produced six homogeneous samples of stars with high-quality astrophysical parameters across the HR diagram for the community to exploit. We first focus on three samples that span a large parameter space: young massive disc stars (OBA; about 3 Million), FGKM spectral type stars (about 3 Million), and UCDs (about 20 000). We provide these sources along with additional information (either a flag or complementary parameters) as tables that are made available in the Gaia archive. We also identify 15 740 bone fide carbon stars and 5863 solar analogues, and provide the first homogeneous set of stellar parameters of the SPSS sample. We demonstrate some applications of these samples in different astrophysical contexts. We use a subset of the OBA sample to illustrate its usefulness in analysing the Milky Way rotation curve. We then use the properties of the FGKM stars to analyse known exoplanet systems. We also analyse the ages of some unseen UCD-companions to the FGKM stars. We additionally predict the colours of the Sun in various passbands (Gaia, 2MASS, WISE) using the solar-analogue sample.Conclusions. Gaia DR3 contains a wealth of new high-quality astrophysical parameters for the community to exploit.
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