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

A Field and Video-annotation Guide for Baited Remote Underwater stereo-video Surveys of Demersal Fish Assemblages

1. Baited remote underwater stereo‐video systems (stereo‐BRUVs) are a popular tool to sample demersal fish assemblages and gather data on their relative abundance and body size structure in a robust, cost‐effective and non‐invasive manner. Given the rapid uptake of the method, subtle differences have emerged in the way stereo‐BRUVs are deployed and how the resulting imagery is annotated. These disparities limit the interoperability of datasets obtained across studies, preventing broadscale insights into the dynamics of ecological systems. 2. We provide the first globally accepted guide for using stereo‐BRUVs to survey demersal fish assemblages and associated benthic habitats. 3. Information on stereo‐BRUVs design, camera settings, field operations and image annotation are outlined. Additionally, we provide links to protocols for data validation, archiving and sharing. 4. Globally, the use of stereo‐BRUVs is spreading rapidly. We provide a standardized protocol that will reduce methodological variation among researchers and encourage the use of Findable, Accessible, Interoperable and Reusable workflows to increase the ability to synthesize global datasets and answer a broad suite of ecological questions

Marriage and Social Boundaries among British Pakistanis

A cosmopolitan environment offers challenges for cultural groups that seek to reproduce themselves in the next generation. British Pakistanis have not seen the kind of breakdown in marriage boundaries that characterizes other post-war migrants to Britain. The article examines how this pattern is linked to commitments to transnational marriage, which promise a source of future remittances to Pakistan. However, the need to maintain these links has exaggerated the importance of religious and moral display for British Pakistanis, and these have wider effects in the policing of social contact with outsiders and the negative portrayal of the sexual morality of non-Pakistanis