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 New Retrospective on Mergers

This paper is based on my keynote address given at the 2006 International Industrial Organization Conference in Boston, April 8, 2006. I survey long-run trends in mergers, review the debate over the economic success of mergers generally, and examine the changing treatment that business schools have accorded mergers over the past five decades. A final section is a time series analysis of links at the U.S. macroeconomic level between changes in merger activity and labor productivity growth. Copyright Springer 2006business schools, efficiency, mergers, productivity,

Chinese citizenship ‘after orientalism’: academic narratives on internal migrants in China

In this article I enquire into the possibility of citizenship ‘after orientalism’ by examining the writing of Chinese academics on internal migrants in China. The popular narratives on migrants represent them as ‘peasant workers in need of becoming urban citizens’. These representations are based on an understanding of citizenship as necessarily urban and modern, which is reminiscent of Weber's theory of citizenship, and is based on mechanisms of ‘internal orientalism’. I argue that contrary to the popular understanding of ‘post-oriental’ as ‘resistance to the West’, it is the process of the boundary-transgression between rural and urban, rather than non-Western ideas of citizenship, that opens space for citizenship ‘after orientalism’ in China. This process of boundary-transgression can be mapped through new practices of naming and narrative-setting in the literature on internal migrants, which emphasise subjective character of group boundaries and appeal for recognition of rural and migrant identities. It is through these instances of boundary-transgression between urban and rural that the orientalism embedded within the notion of citizenship in China is challenged