| 1. |
- Cruz, Raquel, et al.
(författare)
-
Novel genes and sex differences in COVID-19 severity
- 2022
-
Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806
-
Tidskriftsartikel (refereegranskat)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.
|
|
| 2. |
- Roman, Diana, et al.
(författare)
-
Mechanisms of Unrest and Eruption at Persistently Restless Volcanoes: Insights From the 2015 Eruption of Telica Volcano, Nicaragua
- 2019
-
Ingår i: Geochemistry, Geophysics, Geosystems. - 1525-2027. ; 20:8, s. 4162-4183
-
Tidskriftsartikel (refereegranskat)abstract
- Many of Earth's volcanoes experience well-defined states of “quiescence” and “unrest,” with unrest occasionally culminating in eruption. Some volcanoes, however, experience an unusually protracted (i.e., decades-long) period of noneruptive unrest and are thus categorized as “persistently restless volcanoes” (PRVs). The processes that drive persistently restless volcanism are poorly understood, as our knowledge of PRVs is currently based on a small number of case studies. Here we examine multidisciplinary observations of the 2015 eruptive episode at Telica Volcano, Nicaragua, in the context of its long-term behavior. We suggest that the latter phases of the 2015 eruption were ultimately driven by destabilization of its shallow magma reservoir. Based on previous geodetic-seismic studies of Telica (Geirsson et al., 2014, https://doi.org/10.1016/j.jvolgeores.2013.11.009; Rodgers et al., 2013, https://doi.org/10.1016/j.jvolgeores.2013.08.010 and 2015, https://doi.org/10.1016/j.jvolgeores.2014.11.012) and on multiparameter observations at Telica over a 7-year period, we propose that three distinct states of unrest occur at Telica over decadal timescales: a stable open state involving steady conduit convection and two distinct “unstable” states that may lead to eruptions. In the “weak sealing” state, phreatic explosions result from steady conduit convection underlying a weak seal. In the “destabilized” state, destabilization of the top of the convecting magma in the conduit leads to rapid accumulation of high pressures leading to strong/impulsive phreatomagmatic explosions. Our observations and interpretations suggest that continuous seismic, ground-based deformation, gas emission, and thermal monitoring and interpretation of these data within a paradigm of sustained conduit convection modulated by episodes of sealing and destabilization of shallow magma reservoirs may allow robust forecasting of eruption potential, energy, and duration at Telica and similar PRVs worldwide.
|
|
