37 research outputs found
Whole-genome sequencing reveals host factors underlying critical COVID-19
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
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Deriving Snow Depth From ICESat-2 Lidar Multiple Scattering Measurements: Uncertainty Analyses
The application of diffusion theory and Monte Carlo lidar radiative transfer simulations presented in Part I of this series of study suggests that snow depth can be derived from the first-, second- and third-order moments of the lidar backscattering pathlength distribution. These methods are now applied to the satellite ICESat-2 lidar measurements over the Arctic sea ice and land surfaces of Northern Hemisphere. Over the Arctic sea ice, the ICESat-2 retrieved snow depths agree well with co-located IceBridge snow radar measured values with a root-mean-square (RMS) difference of 7.8 cm or 29.2% of the mean snow depth. The terrestrial snow depths derived from ICESat-2 show drastic spatial variation of the snowpack along ICESat-2 ground tracks over the Northern Hemisphere, which are consistent with the University of Arizona (UA) and Canadian Meteorological Centre (CMC) gridded daily snow products. The RMS difference in snow depths between ICESat-2 and UA gridded daily snow products is 14 cm, or 28% of the mean UA snow depth. To better understand these results, we also discuss the possible sources of errors in ICESat-2 derived snow depths, including surface roughness within the laser footprint, atmospheric forward scattering, solar background noise, and detector dark current. Simulation results indicate that the snow depth errors would be less than 5 cm if the standard deviation of pulse spreading due to surface roughness is within 50 cm. Our results demonstrate that the ICESat-2 lidar measurements can be used to reliably derive snow depth, which is a critical geophysical parameter for cryosphere studies including sea ice thickness estimation and also provides important constraints in the modeling of terrestrial hydrological processes. Copyright © 2022 Lu, Hu, Zeng, Stamnes, Neuman, Kurtz, Yang, Zhai, Gao, Sun, Xu, Liu, Omar, Baize, Rogers, Mitchell, Stamnes, Huang, Chen, Weimer, Lee and Fair.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]