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  • Blokland, G. A. M., et al. (författare)
  • Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
  • 2021
  • Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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  • Dornelas, M., et al. (författare)
  • BioTIME: A database of biodiversity time series for the Anthropocene
  • 2018
  • Ingår i: Global Ecology and Biogeography. - 1466-822X. ; 27:7, s. 760-786
  • Tidskriftsartikel (refereegranskat)abstract
    • Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km(2) (158 cm(2)) to 100 km(2) (1,000,000,000,000 cm(2)). Time period and grainBio: TIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.
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  • Marshall, Christian R., et al. (författare)
  • Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
  • 2017
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 49:1, s. 27-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.
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  • Ripke, Stephan, et al. (författare)
  • Biological insights from 108 schizophrenia-associated genetic loci
  • 2014
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 511:7510, s. 421-427
  • Tidskriftsartikel (refereegranskat)abstract
    • Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
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  • Benz, W., et al. (författare)
  • The CHEOPS mission
  • 2021
  • Ingår i: Experimental Astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 51:1, s. 109-151
  • Tidskriftsartikel (refereegranskat)abstract
    • The CHaracterising ExOPlanet Satellite (CHEOPS) was selected on October 19, 2012, as the first small mission (S-mission) in the ESA Science Programme and successfully launched on December 18, 2019, as a secondary passenger on a Soyuz-Fregat rocket from Kourou, French Guiana. CHEOPS is a partnership between ESA and Switzerland with important contributions by ten additional ESA Member States. CHEOPS is the first mission dedicated to search for transits of exoplanets using ultrahigh precision photometry on bright stars already known to host planets. As a follow-up mission, CHEOPS is mainly dedicated to improving, whenever possible, existing radii measurements or provide first accurate measurements for a subset of those planets for which the mass has already been estimated from ground-based spectroscopic surveys. The expected photometric precision will also allow CHEOPS to go beyond measuring only transits and to follow phase curves or to search for exo-moons, for example. Finally, by unveiling transiting exoplanets with high potential for in-depth characterisation, CHEOPS will also provide prime targets for future instruments suited to the spectroscopic characterisation of exoplanetary atmospheres. To reach its science objectives, requirements on the photometric precision and stability have been derived for stars with magnitudes ranging from 6 to 12 in the V band. In particular, CHEOPS shall be able to detect Earth-size planets transiting G5 dwarf stars (stellar radius of 0.9R⊙) in the magnitude range 6 ≤ V ≤ 9 by achieving a photometric precision of 20 ppm in 6 hours of integration time. In the case of K-type stars (stellar radius of 0.7R⊙) of magnitude in the range 9 ≤ V ≤ 12, CHEOPS shall be able to detect transiting Neptune-size planets achieving a photometric precision of 85 ppm in 3 hours of integration time. This precision has to be maintained over continuous periods of observation for up to 48 hours. This precision and stability will be achieved by using a single, frame-transfer, back-illuminated CCD detector at the focal plane assembly of a 33.5 cm diameter, on-axis Ritchey-Chrétien telescope. The nearly 275 kg spacecraft is nadir-locked, with a pointing accuracy of about 1 arcsec rms, and will allow for at least 1 Gbit/day downlink. The sun-synchronous dusk-dawn orbit at 700 km altitude enables having the Sun permanently on the backside of the spacecraft thus minimising Earth stray light. A mission duration of 3.5 years in orbit is foreseen to enable the execution of the science programme. During this period, 20% of the observing time is available to the wider community through yearly ESA call for proposals, as well as through discretionary time approved by ESA’s Director of Science. At the time of this writing, CHEOPS commissioning has been completed and CHEOPS has been shown to fulfill all its requirements. The mission has now started the execution of its science programme.
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  • Lendl, M., et al. (författare)
  • The hot dayside and asymmetric transit of WASP-189 b seen by CHEOPS
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 643
  • Tidskriftsartikel (refereegranskat)abstract
    • The CHEOPS space mission dedicated to exoplanet follow-up was launched in December 2019, equipped with the capacity to perform photometric measurements at the 20 ppm level. As CHEOPS carries out its observations in a broad optical passband, it can provide insights into the reflected light from exoplanets and constrain the short-wavelength thermal emission for the hottest of planets by observing occultations and phase curves. Here, we report the first CHEOPS observation of an occultation, namely, that of the hot Jupiter WASP-189 b, a MP ≈ 2MJ planet orbiting an A-type star. We detected the occultation of WASP-189 b at high significance in individual measurements and derived an occultation depth of dF = 87.9 ± 4.3 ppm based on four occultations. We compared these measurements to model predictions and we find that they are consistent with an unreflective atmosphere heated to a temperature of 3435 ± 27 K, when assuming inefficient heat redistribution. Furthermore, we present two transits of WASP-189 b observed by CHEOPS. These transits have an asymmetric shape that we attribute to gravity darkening of the host star caused by its high rotation rate. We used these measurements to refine the planetary parameters, finding a ~25% deeper transit compared to the discovery paper and updating the radius of WASP-189 b to 1.619 ± 0.021RJ. We further measured the projected orbital obliquity to be λ = 86.4-4.4+2.9°, a value that is in good agreement with a previous measurement from spectroscopic observations, and derived a true obliquity of ψ = 85.4 ± 4.3°. Finally, we provide reference values for the photometric precision attained by the CHEOPS satellite: for the V = 6.6 mag star, and using a 1-h binning, we obtain a residual RMS between 10 and 17 ppm on the individual light curves, and 5.7 ppm when combining the four visits.
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