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- Cruz, Raquel, et al.
(author)
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Novel genes and sex differences in COVID-19 severity
- 2022
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In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
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Journal article (peer-reviewed)abstract
- Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
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2. |
- Cadenas, Patricia, et al.
(author)
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The role of extensional detachment systems in thinning the crust and exhuming granulites : analogies between the offshore Le Danois High and the onshore Labourd Massif in the Biscay/Pyrenean rifts
- 2021
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In: Bulletin de la Société Géologique de France. - : EDP Sciences. - 0037-9409 .- 1777-5817. ; 192
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Journal article (peer-reviewed)abstract
- Large uncertainties remain about the architecture, timing and role of the structures responsible for high degrees of crustal thinning and the exhumation of mid-crustal granulites in the Pyrenean and Biscay rift systems. Both, the Le Danois High in the North Iberian margin and the Labourd Massif in the Western Pyrenees preserve evidence of extensional detachment faults and include exhumed granulites, which are locally reworked in syn-rift sediments. In this study, we compare the crustal structure and its link to the overlying sediments at the two sites based on the interpretation of high quality 2D seismic reflection profiles offshore and field observations and published geological cross-sections onshore. New reported seismic and field observations support that extensional detachment systems delineate the top basement in the Le Danois High and the Labourd Massif, advocating for a similar tectonic evolution. We propose that the Le Danois and North Mauleon extensional detachment systems were responsible for high degrees of crustal thinning and the exhumation of the pre-rift brittle-ductile transition and associated mid-crustal granulites during Aptian to Cenomanian extension, leading to the formation of the Le Danois and Labourd crustal tapers. Subsequently tilted and uplifted during the Alpine convergence, the two taper blocks lay at present in the hanging-wall of major Alpine thrusts. Their position at overlapping, en-echelon hyperextended rift segments at the end of rifting, and the occurrence of shortcutting structures at depth linking neighbouring rift segments can explain the preservation of the rift-related detachment systems. This study proposes for the first time analogies between the offshore Le Danois High and the onshore Labourd Massif and demonstrates the importance of extensional detachment systems in thinning the crust and exhuming mid-crustal granulites at the seafloor in the Biscay and Pyrenean rift systems during Aptian to Cenomanian extension.
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3. |
- Frasca, Gianluca, et al.
(author)
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A kinematic reconstruction of Iberia using intracontinental strike-slip corridors
- 2021
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In: Terra Nova. - : John Wiley & Sons. - 0954-4879 .- 1365-3121. ; 33:6, s. 573-581
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Journal article (peer-reviewed)abstract
- Despite considerable progress in restoring rifted margins, none of the current kinematic models can restore the Mesozoic motion of the Iberian block in full agreement with the circum-Iberian geology. This conflict requires a revision of the kinematic description at the onset of divergence. The circum-Iberian region has a unique geological dataset that allows calibration and testing of kinematic reconstructions and therefore it is an ideal candidate for testing intracontinental restoration approaches. Here we define intracontinental deforming regions, referred to as strike-slip corridors, based on alignments of Mesozoic rift basins and/or transfer zones bordering rigid continental blocks. We use these strike-slip corridors and data from the southern N-Atlantic and Tethys to define the motion path of the Flemish Cap, Ebro and Iberia continental blocks. The resulting Mesozoic kinematic model for the Iberian block is compatible with recently published data and interpretations describing the Mesozoic circum-Iberian geology. Large-scale intracontinental strike-slip corridors may offer a valid boundary condition for reconstructing continental block motion at the onset of divergence in intracontinental settings.
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4. |
- Manatschal, Gianreto, et al.
(author)
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The role of inheritance in forming rifts and rifted margins and building collisional orogens : a Biscay-Pyrenean perspective
- 2021
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In: Bulletin de la Société Géologique de France. - : EDP Sciences. - 0037-9409 .- 1777-5817. ; 192
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Journal article (peer-reviewed)abstract
- A long-standing challenge in tectonics is to evaluate the role of inheritance and define the initial conditions of a geodynamic system, which are prerequisites to understand and model its evolution with some accuracy. Here we revisit the concept of "inheritance" by distinguishing "interface shape inheritance", which includes the transient thermal state and gravitational potential energy, and "persisting inheritance", which encompasses long-lasting structural and compositional inheritance. This new approach allows us to investigate, at each stage of a Wilson Cycle, the interplay between inheritance (innate/"genetic code") and the physical processes at play (extension/compression, magmatism etc.). The aim of this paper is to provide a conceptual framework that integrates the role of inheritance in the study of rifts, rifted margins and collisional orogens based on the work done in the OROGEN project, which focuses on the Biscay-Pyrenean system. The Biscay-Pyrenean rift system resulted from a multistage rift evolution that developed over a complex lithosphere pre-structured by the Variscan orogenic cycle. There is a general agreement that the Pyrenean-Cantabrian orogen resulted from the reactivation of an increasingly mature rift system along-strike, ranging from mature rifted margins in the west to an immature and segmented hyperextended rift in the east. However, different models have been proposed to explain the preceding rifting and its influence on the subsequent reactivation. Results from the OROGEN project highlight the sequential reactivation of rift-inherited decoupling horizons and identify the specific role of exhumed mantle, hyperextended and necking domains during compressional reactivation. They also highlight the contrasting fate of rift segment centres versus segment boundaries during convergence, explaining the non-cylindricity of internal parts of collisional orogens. Results from the OROGEN project also suggest that the role of inheritance is more important during the initial stages of collision, which may explain the higher complexity of internal parts of orogenic systems with respect to their external parts. In contrast, when the system involved in the orogeny is more mature, the orogenic evolution is mostly controlled by first-order physical processes as described in the Coulomb Wedge theory, for instance. This may account for the simpler and more continuous architecture of external parts of collisional orogens and may also explain why most numerical models can reproduce mature orogenic architectures with a better accuracy compared to those of initial collisional stages. The new concepts developed from the OROGEN research are now ready to be tested at other orogenic systems that result from the reactivation of rifted margins, such as the Alps, the Colombian cordilleras and the Caribbean, Taiwan, Oman, Zagros or Timor.
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