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

Geochemical mapping using stream sediments in west-central Nigeria : implications for environmental studies and mineral exploration in West Africa

This paper provides an overview of regional geochemical mapping using stream sediments from central and south-western Nigeria. A total of 1569 stream sediment samples were collected and 54 major and trace elements determined by ICP-MS and Au, Pd and Pt by fire assay. Multivariate statistical techniques (e.g., correlation analysis and principal factor analysis) were used to explore the data, following appropriate data transformation, to understand the data structure, investigate underlying processes controlling spatial geochemical variability and identify element associations. Major geochemical variations are controlled by source geology and provenance, as well as chemical weathering and winnowing processes, more subtle variations are a result of land use and contamination from anthropogenic activity. This work has identified placer deposits of potential economic importance for Au, REE, Ta, Nb, U and Pt, as well as other primary metal deposits. Areas of higher As and Cr (>2 mg/kg and >70 mg/kg respectively) are associated with Mesozoic and younger coastal sediments in SW Nigeria. High stream sediment Zr concentrations (mean>0.2%), from proximal zircons derived from weathering of basement rocks, have important implications for sample preparation and subsequent analysis due to interferences. Associated heavy minerals enriched in high field strength elements, and notably rare earths’, may also have important implications for understanding magmatic processes within the basement terrain of West Africa. This study provides important new background/baseline geochemical values for common geological domains in Nigeria (which extend across other parts of West Africa) for assessment of contamination from urban/industrial land use changes and mining activities. Regional stream sediment mapping is also able to provide important new information with applications across a number of sectors including agriculture, health, land use and planning

Genotype by environment studies across Australia reveal the importance of phenology for chickpea (Cicer arietinum L.) improvement

Chickpea (Cicer arietinum L.) genotypes comprising released cultivars, advanced breeding lines, and landraces of Australian, Mediterranean basin, Indian, and Ethiopian origin were evaluated at 5 representative sites (Merredin, WA; Minnipa, SA; Walpeup, Vic.; Tamworth, NSW; Warwick, Qld) over 2 years. Data on plant stand, early vigour, phenology, productivity, and yield components were collected at each site. Site yields ranged from 0.3 t/ha at Minnipa in 1999 to 3.5 t/ha at Warwick in 1999. Genotype by environment (G × E) interaction was highly significant. Principal components analysis revealed contrasting genotype interaction behaviour at dry, low-yielding sites (Minnipa 1999, Merredin 2000) and higher rainfall, longer growing-season environments (Tamworth 2000). Genotype clusters performing well under stress tended to yield well at all sites except Tamworth in 2000, and were characterised by early phenology and high harvest index, but were not different in terms of biomass or early vigour. Some of these traits were strongly influenced by germplasm origin. The material with earliest phenology came from Ethiopia, and southern and central India, with progressively later material from northern India and Australia, and finally the Mediterranean. There was a delay between the onset of flowering and podding at all sites, which was related to average temperatures immediately post-anthesis (r = –0.81), and therefore larger in early flowering material (>30 days at some sites). Harvest index was highest in Indian and Ethiopian germplasm, whereas crop height was greatest in Australian and Mediterranean accessions. Some consistently high yielding genotypes new to the Australian breeding program were identified (ICCV 10, BG 362), and the existing cultivar Lasseter was also confirmed to be very productive