1. |
- 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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2. |
- Brown, A. G. A., et al.
(author)
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Gaia Data Release 1 Summary of the astrometric, photometric, and survey properties
- 2016
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
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Journal article (peer-reviewed)abstract
- Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues - a realisation of the Tycho-Gaia Astrometric Solution (TGAS) - and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of similar to 3000 Cepheid and RR Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr(-1) for the proper motions. A systematic component of similar to 0.3 mas should be added to the parallax uncertainties. For the subset of similar to 94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr(-1). For the secondary astrometric data set, the typical uncertainty of the positions is similar to 10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to similar to 0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data.
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3. |
- Prusti, T., et al.
(author)
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The Gaia mission
- 2016
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
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Journal article (peer-reviewed)abstract
- Gaia is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
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4. |
- Clementini, G., et al.
(author)
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Testing parallaxes with local Cepheids and RR Lyrae stars
- 2017
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605
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Journal article (peer-reviewed)abstract
- Context. Parallaxes for 331 classical Cepheids, 31 Type II Cepheids, and 364 RR Lyrae stars in common between Gaia and the HIPPARCOS and Tycho-2 catalogues are published in Gaia Data Release 1 (DR1) as part of the Tycho-Gaia Astrometric Solution (TGAS). Aims. In order to test these first parallax measurements of the primary standard candles of the cosmological distance ladder, which involve astrometry collected by Gaia during the initial 14 months of science operation, we compared them with literature estimates and derived new period-luminosity (PL), period-Wesenheit (PW) relations for classical and Type II Cepheids and infrared PL, PL-metallicity (PLZ), and optical luminosity-metallicity (MV-[Fe/H]) relations for the RR Lyrae stars, with zero points based on TGAS.Methods. Classical Cepheids were carefully selected in order to discard known or suspected binary systems. The final sample comprises 102 fundamental mode pulsators with periods ranging from 1.68 to 51.66 days (of which 33 with sigma(omega)/omega < 0 : 5). The Type II Cepheids include a total of 26 W Virginis and BL Herculis stars spanning the period range from 1.16 to 30.00 days (of which only 7 with sigma(omega)/omega 0 : 5). The RR Lyrae stars include 200 sources with pulsation period ranging from 0.27 to 0.80 days (of which 112 with sigma(omega)/omega < 0 : 5). The new relations were computed using multi- band (V; I; J; K-s) photometry and spectroscopic metal abundances available in the literature, and by applying three alternative approaches: (i) linear least-squares fitting of the absolute magnitudes inferred from direct transformation of the TGAS parallaxes; (ii) adopting astrometry-based luminosities; and (iii) using a Bayesian fitting approach. The last two methods work in parallax space where parallaxes are used directly, thus maintaining symmetrical errors and allowing negative parallaxes to be used. The TGAS-based PL; PW; PLZ, and MV [Fe/H] relations are discussed by comparing the distance to the Large Magellanic Cloud provided by different types of pulsating stars and alternative fitting methods.Results. Good agreement is found from direct comparison of the parallaxes of RR Lyrae stars for which both TGAS and HST measurements are available. Similarly, very good agreement is found between the TGAS values and the parallaxes inferred from the absolute magnitudes of Cepheids and RR Lyrae stars analysed with the Baade-Wesselink method. TGAS values also compare favourably with the parallaxes inferred by theoretical model fitting of the multi-band light curves for two of the three classical Cepheids and one RR Lyrae star, which were analysed with this technique in our samples. The K-band PL relations show the significant improvement of the TGAS parallaxes for Cepheids and RR Lyrae stars with respect to the HIPPARCOS measurements. This is particularly true for the RR Lyrae stars for which improvement in quality and statistics is impressive.Conclusions. TGAS parallaxes bring a significant added value to the previous HIPPARCOS estimates. The relations presented in this paper represent the first Gaia-calibrated relations and form a work-in-progress milestone report in the wait for Gaia-only parallaxes of which a first solution will become available with Gaia Data Release 2 (DR2) in 2018.
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5. |
- Jiang, X., et al.
(author)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Journal article (peer-reviewed)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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6. |
- Babusiaux, C., et al.
(author)
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Observational Hertzsprung-Russell diagrams
- 2018
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
-
Journal article (peer-reviewed)abstract
- Context. Gaia Data Release 2 provides high-precision astrometry and three-band photometry for about 1.3 billion sources over the full sky. The precision, accuracy, and homogeneity of both astrometry and photometry are unprecedented. Aims. We highlight the power of the Gaia DR2 in studying many fine structures of the Hertzsprung-Russell diagram (HRD). Gaia allows us to present many different HRDs, depending in particular on stellar population selections. We do not aim here for completeness in terms of types of stars or stellar evolutionary aspects. Instead, we have chosen several illustrative examples. Methods. We describe some of the selections that can be made in Gaia DR2 to highlight the main structures of the Gaia HRDs. We select both field and cluster (open and globular) stars, compare the observations with previous classifications and with stellar evolutionary tracks, and we present variations of the Gaia HRD with age, metallicity, and kinematics. Late stages of stellar evolution such as hot subdwarfs, post-AGB stars, planetary nebulae, and white dwarfs are also analysed, as well as low-mass brown dwarf objects. Results. The Gaia HRDs are unprecedented in both precision and coverage of the various Milky Way stellar populations and stellar evolutionary phases. Many fine structures of the HRDs are presented. The clear split of the white dwarf sequence into hydrogen and helium white dwarfs is presented for the first time in an HRD. The relation between kinematics and the HRD is nicely illustrated. Two different populations in a classical kinematic selection of the halo are unambiguously identified in the HRD. Membership and mean parameters for a selected list of open clusters are provided. They allow drawing very detailed cluster sequences, highlighting fine structures, and providing extremely precise empirical isochrones that will lead to more insight in stellar physics. Conclusions. Gaia DR2 demonstrates the potential of combining precise astrometry and photometry for large samples for studies in stellar evolution and stellar population and opens an entire new area for HRD-based studies.
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7. |
- Brown, A. G. A., et al.
(author)
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Gaia Data Release 2 Summary of the contents and survey properties
- 2018
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
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Journal article (peer-reviewed)abstract
- Context. We present the second Gaia data release, Gaia DR2, consisting of astrometry, photometry, radial velocities, and information on astrophysical parameters and variability, for sources brighter than magnitude 21. In addition epoch astrometry and photometry are provided for a modest sample of minor planets in the solar system. Aims. A summary of the contents of Gaia DR2 is presented, accompanied by a discussion on the differences with respect to Gaia DR1 and an overview of the main limitations which are still present in the survey. Recommendations are made on the responsible use of Gaia DR2 results. Methods. The raw data collected with the Gaia instruments during the first 22 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into this second data release, which represents a major advance with respect to Gaia DR1 in terms of completeness, performance, and richness of the data products. Results. Gaia DR2 contains celestial positions and the apparent brightness in G for approximately 1.7 billion sources. For 1.3 billion of those sources, parallaxes and proper motions are in addition available. The sample of sources for which variability information is provided is expanded to 0 : 5 million stars. This data release contains four new elements: broad-band colour information in the form of the apparent brightness in the G(BP) (330-680 nm) and G(RP) (630-1050 nm) bands is available for 1.4 billion sources; median radial velocities for some 7 million sources are presented; for between 77 and 161 million sources estimates are provided of the stellar effective temperature, extinction, reddening, and radius and luminosity; and for a pre-selected list of 14 000 minor planets in the solar system epoch astrometry and photometry are presented. Finally, Gaia DR2 also represents a new materialisation of the celestial reference frame in the optical, the Gaia-CRF2, which is the first optical reference frame based solely on extragalactic sources. There are notable changes in the photometric system and the catalogue source list with respect to Gaia DR1, and we stress the need to consider the two data releases as independent. Conclusions. Gaia DR2 represents a major achievement for the Gaia mission, delivering on the long standing promise to provide parallaxes and proper motions for over 1 billion stars, and representing a first step in the availability of complementary radial velocity and source astrophysical information for a sample of stars in the Gaia survey which covers a very substantial fraction of the volume of our galaxy.
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8. |
- Helmi, A., et al.
(author)
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Gaia Data Release 2 Kinematics of globular clusters and dwarf galaxies around the Milky Way
- 2018
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616:A12
-
Journal article (peer-reviewed)abstract
- Aims The goal of this paper is to demonstrate the outstanding quality of the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way. We focus here on determining the proper motions of 75 Galactic globular clusters, nine dwarf spheroidal galaxies, one ultra-faint system, and the Large and Small Magellanic Clouds.Methods Using data extracted from the Gaia archive, we derived the proper motions and parallaxes for these systems, as well as their uncertainties. We demonstrate that the errors, statistical and systematic, are relatively well understood. We integrated the orbits of these objects in three different Galactic potentials, and characterised their properties. We present the derived proper motions, space velocities, and characteristic orbital parameters in various tables to facilitate their use by the astronomical community.Results Our limited and straightforward analyses have allowed us for example to (i) determine absolute and very precise proper motions for globular clusters; (ii) detect clear rotation signatures in the proper motions of at least five globular clusters; (iii) show that the satellites of the Milky Way are all on high-inclination orbits, but that they do not share a single plane of motion; (i v) derive a lower limit for the mass of the Milky Way of 9.1(-2.6)(+6.2) x 10(11) M-circle dot based on the assumption that the Leo I dwarf spheroidal is bound; (v) derive a rotation curve for the Large Magellanic Cloud based solely on proper motions that is competitive with line-of-sight velocity curves, now using many orders of magnitude more sources; and (v i) unveil the dynamical effect of the bar on the motions of stars in the Large Magellanic Cloud.Conclusions All these results highlight the incredible power of the Gaia astrometric mission, and in particular of its second data release.
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9. |
- Katz, D., et al.
(author)
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Gaia Data Release 2 Mapping the Milky Way disc kinematics
- 2018
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
-
Journal article (peer-reviewed)abstract
- Context. The second Gaia data release (Gaia DR2) contains high-precision positions, parallaxes, and proper motions for 1.3 billion sources as well as line-of-sight velocities for 7.2 million stars brighter than G(RVS) = 12 mag. Both samples provide a full sky coverage. Aims. To illustrate the potential of Gaia DR2, we provide a first look at the kinematics of the Milky Way disc, within a radius of several kiloparsecs around the Sun. Methods. We benefit for the first time from a sample of 6.4 million F-G-K stars with full 6D phase-space coordinates, precise parallaxes (sigma((omega) over bar)/(omega) over bar <= 20%), and precise Galactic cylindrical velocities (median uncertainties of 0.9-1.4 km s(-1) and 20% of the stars with uncertainties smaller than 1 km s(-1) on all three components). From this sample, we extracted a sub-sample of 3.2 million giant stars to map the velocity field of the Galactic disc from similar to 5 kpc to similar to 13 kpc from the Galactic centre and up to 2 kpc above and below the plane. We also study the distribution of 0.3 million solar neighbourhood stars (r < 200 pc), with median velocity uncertainties of 0.4 km s(-1), in velocity space and use the full sample to examine how the over-densities evolve in more distant regions. Results. Gaia DR2 allows us to draw 3D maps of the Galactocentric median velocities and velocity dispersions with unprecedented accuracy, precision, and spatial resolution. The maps show the complexity and richness of the velocity field of the galactic disc. We observe streaming motions in all the components of the velocities as well as patterns in the velocity dispersions. For example, we confirm the previously reported negative and positive galactocentric radial velocity gradients in the inner and outer disc, respectively. Here, we see them as part of a non-axisymmetric kinematic oscillation, and we map its azimuthal and vertical behaviour. We also witness a new global arrangement of stars in the velocity plane of the solar neighbourhood and in distant regions in which stars are organised in thin substructures with the shape of circular arches that are oriented approximately along the horizontal direction in the U - V plane. Moreover, in distant regions, we see variations in the velocity substructures more clearly than ever before, in particular, variations in the velocity of the Hercules stream. Conclusions. Gaia DR2 provides the largest existing full 6D phase-space coordinates catalogue. It also vastly increases the number of available distances and transverse velocities with respect to Gaia DR1. Gaia DR2 offers a great wealth of information on the Milky Way and reveals clear non-axisymmetric kinematic signatures within the Galactic disc, for instance. It is now up to the astronomical community to explore its full potential.
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10. |
- Mignard, F., et al.
(author)
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Gaia Data Release 2 The celestial reference frame (Gaia-CRF2)
- 2018
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In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 616
-
Journal article (peer-reviewed)abstract
- Context: The second release of Gaia data (Gaia DR2) contains the astrometric parameters for more than half a million quasars. This set defines a kinematically non-rotating reference frame in the optical domain. A subset of these quasars have accurate VLBI positions that allow the axes of the reference frame to be aligned with the International Celestial Reference System (ICRF) radio frame.Aims: We describe the astrometric and photometric properties of the quasars that were selected to represent the celestial reference frame of Gaia DR2 (Gaia-CRF2), and to compare the optical and radio positions for sources with accurate VLBI positions.Methods: Descriptive statistics are used to characterise the overall properties of the quasar sample. Residual rotation and orientation errors and large-scale systematics are quantified by means of expansions in vector spherical harmonics. Positional differences are calculated relative to a prototype version of the forthcoming ICRF3.Results: Gaia-CRF2 consists of the positions of a sample of 556 869 sources in Gaia DR2, obtained from a positional cross-match with the ICRF3-prototype and AllWISE AGN catalogues. The sample constitutes a clean, dense, and homogeneous set of extragalactic point sources in the magnitude range G similar or equal to 16 to 21 mag with accurately known optical positions. The median positional uncertainty is 0.12 mas for G < 18 mag and 0.5 mas at G = 20 mag. Large-scale systematics are estimated to be in the range 20 to 30 mu as. The accuracy claims are supported by the parallaxes and proper motions of the quasars in Gaia DR2. The optical positions for a subset of 2820 sources in common with the ICRF3-prototype show very good overall agreement with the radio positions, but several tens of sources have significantly discrepant positions.Conclusions: Based on less than 40% of the data expected from the nominal Gaia mission, Gaia-CRF2 is the first realisation of a non-rotating global optical reference frame that meets the ICRS prescriptions, meaning that it is built only on extragalactic sources. Its accuracy matches the current radio frame of the ICRF, but the density of sources in all parts of the sky is much higher, except along the Galactic equator.
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11. |
- Spoto, F., et al.
(author)
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Gaia Data Release 2 : Observations of solar system objects
- 2018
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In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 616
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Journal article (peer-reviewed)abstract
- Context: The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations.Aims: We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality.Methods: To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP).Results: The overall astrometric performance is close to the expectations, with an optimal range of brightness G similar to 12 - 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G similar to 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.
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12. |
- Drimmel, R., et al.
(author)
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Gaia Data Release 3: Mapping the asymmetric disc of the Milky Way
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)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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13. |
- Montegriffo, P., et al.
(author)
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Gaia Data Release 3: The Galaxy in your preferred colours: Synthetic photometry from Gaia low-resolution spectra
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Gaia Data Release 3 provides novel flux-calibrated low-resolution spectrophotometry for ≅220 million sources in the wavelength range 330 nm ≤ λ ≤ 1050 nm (XP spectra). Synthetic photometry directly tied to a flux in physical units can be obtained from these spectra for any passband fully enclosed in this wavelength range. We describe how synthetic photometry can be obtained from XP spectra, illustrating the performance that can be achieved under a range of different conditions - for example passband width and wavelength range - as well as the limits and the problems affecting it. Existing top-quality photometry can be reproduced within a few per cent over a wide range of magnitudes and colour, for wide and medium bands, and with up to millimag accuracy when synthetic photometry is standardised with respect to these external sources. Some examples of potential scientific application are presented, including the detection of multiple populations in globular clusters, the estimation of metallicity extended to the very metal-poor regime, and the classification of white dwarfs. A catalogue providing standardised photometry for ≅2.2×108 sources in several wide bands of widely used photometric systems is provided (Gaia Synthetic Photometry Catalogue; GSPC) as well as a catalogue of ≅105 white dwarfs with DA/non-DA classification obtained with a Random Forest algorithm (Gaia Synthetic Photometry Catalogue for White Dwarfs; GSPC-WD).
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14. |
- De Ridder, J., et al.
(author)
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Gaia Data Release 3: Pulsations in main sequence OBAF-type stars
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)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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15. |
- Galluccio, L., et al.
(author)
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Gaia Data Release 3: Reflectance spectra of Solar System small bodies
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)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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16. |
- Lindegren, L., et al.
(author)
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Gaia Data Release 3: A golden sample of astrophysical parameters
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)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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17. |
- Vallenari, A., et al.
(author)
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Gaia Data Release 3: Summary of the content and survey properties
- 2023
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 674
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Journal article (peer-reviewed)abstract
- Context. We present the third data release of the European Space Agency's Gaia mission, Gaia DR3. This release includes a large variety of new data products, notably a much expanded radial velocity survey and a very extensive astrophysical characterisation of Gaia sources.Aims. We outline the content and the properties of Gaia DR3, providing an overview of the main improvements in the data processing in comparison with previous data releases (where applicable) and a brief discussion of the limitations of the data in this release.Methods. The Gaia DR3 catalogue is the outcome of the processing of raw data collected with the Gaia instruments during the first 34 months of the mission by the Gaia Data Processing and Analysis Consortium.Results. The Gaia DR3 catalogue contains the same source list, celestial positions, proper motions, parallaxes, and broad band photometry in the G, GBP, and G(RP) pass-bands already present in the Early Third Data Release, Gaia EDR3. Gaia DR3 introduces an impressive wealth of new data products. More than 33 million objects in the ranges G(RVS) < 14 and 3100 < T-eff < 14 500, have new determinations of their mean radial velocities based on data collected by Gaia. We provide GRVS magnitudes for most sources with radial velocities, and a line broadening parameter is listed for a subset of these. Mean Gaia spectra are made available to the community. The Gaia DR3 catalogue includes about 1 million mean spectra from the radial velocity spectrometer, and about 220 million low-resolution blue and red prism photometer BP /RP mean spectra. The results of the analysis of epoch photometry are provided for some 10 million sources across 24 variability types. Gaia DR3 includes astrophysical parameters and source class probabilities for about 470 million and 1500 million sources, respectively, including stars, galaxies, and quasars. Orbital elements and trend parameters are provided for some 800 000 astrometric, spectroscopic and eclipsing binaries. More than 150 000 Solar System objects, including new discoveries, with preliminary orbital solutions and individual epoch observations are part of this release. Reflectance spectra derived from the epoch BP /RP spectral data are published for about 60 000 asteroids. Finally, an additional data set is provided, namely the Gaia Andromeda Photometric Survey, consisting of the photometric time series for all sources located in a 5:5 degree radius field centred on the Andromeda galaxy.Conclusions. This data release represents a major advance with respect to Gaia DR2 and Gaia EDR3 because of the unprecedented quantity, quality, and variety of source astrophysical data. To date this is the largest collection of all-sky spectrophotometry, radial velocities, variables, and astrophysical parameters derived from both low- and high-resolution spectra and includes a spectrophotometric and dynamical survey of SSOs of the highest accuracy. The non-single star content surpasses the existing data by orders of magnitude. The quasar host and galaxy light profile collection is the first such survey that is all sky and space based. The astrophysical information provided in Gaia DR3 will unleash the full potential of Gaia's exquisite astrometric, photometric, and radial velocity surveys.
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19. |
- Bruzzi, M, et al.
(author)
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Radiation-hard semiconductor detectors for SuperLHC
- 2005
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 541:1-2, s. 189-201
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Journal article (peer-reviewed)abstract
- An option of increasing the luminosity of the Large Hadron Collider (LHC) at CERN to 1035 cm-2 s-1 has been envisaged to extend the physics reach of the machine. An efficient tracking down to a few centimetres from the interaction point will be required to exploit the physics potential of the upgraded LHC. As a consequence, the semiconductor detectors close to the interaction region will receive severe doses of fast hadron irradiation and the inner tracker detectors will need to survive fast hadron fluences of up to above 1016cm-2. The CERN-RD50 project "Development of Radiation Hard Semiconductor Devices for Very High Luminosity Colliders" has been established in 2002 to explore detector materials and technologies that will allow to operate devices up to, or beyond, this limit. The strategies followed by RD50 to enhance the radiation tolerance include the development of new or defect engineered detector materials (SiC, GaN, Czochralski and epitaxial silicon, oxygen enriched Float Zone silicon), the improvement of present detector designs and the understanding of the microscopic defects causing the degradation of the irradiated detectors. The latest advancements within the RD50 collaboration on radiation hard semiconductor detectors will be reviewed and discussed in this work.
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29. |
- Gusev, A, et al.
(author)
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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
- 2016
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10979-
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Journal article (peer-reviewed)abstract
- Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
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32. |
- Wang, Zhaoming, et al.
(author)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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34. |
- Dadaev, T, et al.
(author)
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Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
- 2018
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2256-
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Journal article (peer-reviewed)abstract
- Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
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39. |
- Turcot, Valerie, et al.
(author)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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41. |
- Do, Ron, et al.
(author)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Journal article (peer-reviewed)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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42. |
- Dork, T, et al.
(author)
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Two truncating variants in FANCC and breast cancer risk
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 12524-
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Journal article (peer-reviewed)abstract
- Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
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43. |
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44. |
- Helbig, K. L., et al.
(author)
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De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
- 2018
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 103:5, s. 666-678
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Journal article (peer-reviewed)abstract
- Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
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45. |
- Marouli, Eirini, et al.
(author)
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Rare and low-frequency coding variants alter human adult height
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Journal article (peer-reviewed)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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48. |
- Surendran, Praveen, et al.
(author)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Journal article (peer-reviewed)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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49. |
- Willer, Cristen J., et al.
(author)
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Discovery and refinement of loci associated with lipid levels
- 2013
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Journal article (peer-reviewed)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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