| 1. |
- Clementini, G., et al.
(författare)
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Testing parallaxes with local Cepheids and RR Lyrae stars
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Brown, A. G. A., et al.
(författare)
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Gaia Data Release 1 Summary of the astrometric, photometric, and survey properties
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
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Tidskriftsartikel (refereegranskat)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.
(författare)
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The Gaia mission
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
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Tidskriftsartikel (refereegranskat)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. |
- van Leeuwen, F., et al.
(författare)
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Gaia Data Release 1 : Open cluster astrometry: Performance, limitations, and future prospects
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 601
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Tidskriftsartikel (refereegranskat)abstract
- Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs.
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| 5. |
- Brown, A. G. A., et al.
(författare)
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Gaia Data Release 2 Summary of the contents and survey properties
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Katz, D., et al.
(författare)
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Gaia Data Release 2 Mapping the Milky Way disc kinematics
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Spoto, F., et al.
(författare)
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Gaia Data Release 2 : Observations of solar system objects
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 616
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Eyer, L., et al.
(författare)
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Gaia Data Release 2 Variable stars in the colour-absolute magnitude diagram
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623
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Tidskriftsartikel (refereegranskat)abstract
- Context. The ESA Gaia mission provides a unique time-domain survey for more than 1.6 billion sources with G less than or similar to 21 mag. Aims. We showcase stellar variability in the Galactic colour-absolute magnitude diagram (CaMD). We focus on pulsating, eruptive, and cataclysmic variables, as well as on stars that exhibit variability that is due to rotation and eclipses. Methods. We describe the locations of variable star classes, variable object fractions, and typical variability amplitudes throughout the CaMD and show how variability-related changes in colour and brightness induce "motions". To do this, we use 22 months of calibrated photometric, spectro-photometric, and astrometric Gaia data of stars with a significant parallax. To ensure that a large variety of variable star classes populate the CaMD, we crossmatched Gaia sources with known variable stars. We also used the statistics and variability detection modules of the Gaia variability pipeline. Corrections for interstellar extinction are not implemented in this article. Results. Gaia enables the first investigation of Galactic variable star populations in the CaMD on a similar, if not larger, scale as was previously done in the Magellanic Clouds. Although the observed colours are not corrected for reddening, distinct regions are visible in which variable stars occur. We determine variable star fractions to within the current detection thresholds of Gaia. Finally, we report the most complete description of variability-induced motion within the CaMD to date. Conclusions. Gaia enables novel insights into variability phenomena for an unprecedented number of stars, which will benefit the understanding of stellar astrophysics. The CaMD of Galactic variable stars provides crucial information on physical origins of variability in a way that has previously only been accessible for Galactic star clusters or external galaxies. Future Gaia data releases will enable significant improvements over this preview by providing longer time series, more accurate astrometry, and additional data types (time series BP and RP spectra, RVS spectra, and radial velocities), all for much larger samples of stars.
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| 9. |
- Helmi, A., et al.
(författare)
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Gaia Data Release 2 Kinematics of globular clusters and dwarf galaxies around the Milky Way
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616:A12
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Mignard, F., et al.
(författare)
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Gaia Data Release 2 The celestial reference frame (Gaia-CRF2)
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 616
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Tidskriftsartikel (refereegranskat)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. |
- Babusiaux, C., et al.
(författare)
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Observational Hertzsprung-Russell diagrams
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
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Tidskriftsartikel (refereegranskat)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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| 19. |
- Matuozzo, D, et al.
(författare)
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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- 2022
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2],P=2.1×10−4). Adding the recently reportedTYK2COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4];P=3.4×10−3). When these 14 loci andTLR7were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0],P=4.7×10−7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9],P=0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years;P=1.68×10−5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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| 20. |
- Bach, D, et al.
(författare)
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Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6
- 2005
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:9, s. 2685-2693
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Tidskriftsartikel (refereegranskat)abstract
- The primary gene mutated in Charcot-Marie-Tooth type 2A is mitofusin-2 (Mfn2). Mfn2 encodes a mitochondrial protein that participates in the maintenance of the mitochondrial network and that regulates mitochondrial metabolism and intracellular signaling. The potential for regulation of human Mfn2 gene expression in vivo is largely unknown. Based on the presence of mitochondrial dysfunction in insulin-resistant conditions, we have examined whether Mfn2 expression is dysregulated in skeletal muscle from obese or nonobese type 2 diabetic subjects, whether muscle Mfn2 expression is regulated by body weight loss, and the potential regulatory role of tumor necrosis factor (TNF)α or interleukin-6. We show that mRNA concentration of Mfn2 is decreased in skeletal muscle from both male and female obese subjects. Muscle Mfn2 expression was also reduced in lean or in obese type 2 diabetic patients. There was a strong negative correlation between the Mfn2 expression and the BMI in nondiabetic and type 2 diabetic subjects. A positive correlation between the Mfn2 expression and the insulin sensitivity was also detected in nondiabetic and type 2 diabetic subjects. To determine the effect of weight loss on Mfn2 mRNA expression, six morbidly obese subjects were subjected to weight loss by bilio-pancreatic diversion. Mean expression of muscle Mfn2 mRNA increased threefold after reduction in body weight, and a positive correlation between muscle Mfn2 expression and insulin sensitivity was again detected. In vitro experiments revealed an inhibitory effect of TNFα or interleukin-6 on Mfn2 expression in cultured cells. We conclude that body weight loss upregulates the expression of Mfn2 mRNA in skeletal muscle of obese humans, type 2 diabetes downregulates the expression of Mfn2 mRNA in skeletal muscle, Mfn2 expression in skeletal muscle is directly proportional to insulin sensitivity and is inversely proportional to the BMI, TNFα and interleukin-6 downregulate Mfn2 expression and may participate in the dysregulation of Mfn2 expression in obesity or type 2 diabetes, and the in vivo modulation of Mfn2 mRNA levels is an additional level of regulation for the control of muscle metabolism and could provide a molecular mechanism for alterations in mitochondrial function in obesity or type 2 diabetes.
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| 23. |
- Manry, Jérémy, et al.
(författare)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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- Matuozzo, Daniela, et al.
(författare)
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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
- 2023
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Ingår i: Genome medicine. - 1756-994X. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in~80% of cases.We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1×10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1×10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4×10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7×10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68×10-5).Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60years old.
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- Vallée, Tanja C, et al.
(författare)
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Wiskott-Aldrich Syndrome: A study on 577 patients defining the genotype as a predictive biomarker for disease severity.
- 2024
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Ingår i: Blood. - 1528-0020.
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Tidskriftsartikel (refereegranskat)abstract
- WAS is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% CI 78-87) at 15 years and 70% (61-80) at 30 years of age. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hotspot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared to 71% (62-81) and 48% (34-68) in patients with any other variant (class II; p<0.0001). The cumulative incidence rates of disease-related complications such as severe bleeding (p=0.007), life-threatening infection (p<0.0001), and autoimmunity (p=0.004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (p=0.6) was not different between classes I and II. This study represents the largest cohort of WAS patients studied so far. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of variant is a biomarker to predict the outcome for WAS patients.
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