14 research outputs found

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    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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    1 fig. 3 tab. 22 ref. Sum. (En)Itchgrass (Rottboellia cochinchinensis) is a serious and persistent weed problem in many tropical agricultural and conservation areas. In Central America it is one of the most noxious and serious weeds in several upland crops, causing severe yield losses. Experimentally, pre-emergence control with herbicides, weed elimination during the fallow period and zero tillage reduced itchgrass populations in comparison to conventional practices used growers (no fallow management, soil preparation by disc harrowing and limited use of in-crop herbicides. Additional improvement in itchgrass management is brought about by inter-sowing legume cover crops. Of several legumes evaluated, mucuna (Mucuna deeringiana) and Canavalia ensiformis controlled the weed better and covered the soil, especially if planted simultaneously with maize. Itchgrass suppression by mucuna usually corresponded with increased grain yields but competition by the cover crop could reduce yields a good compromise is to delay mucuna planting by two weeks in relation to maize. Integrated tactics to control itchgrass were evaluated in on-farm validation plots. Pendimethalin controlled itchgrass at the onset of validation plots and facilitated the establishment of the cover crop. Itchgrass densities were lower in validation plots than in grower's fields while infestation levels and the soil seed bank decreased over three years with integrated management. In general, corn yields were also higher in validation plots. Integrated itchgrass management also proved economically feasible for smallholders. A promising alternative is biological control with the itchgrass smut, Sporisorium ophiuru, which prevents seed set and its host specifi
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