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

Education in Tokugawa Japan

xxiii, 346 hlm.; 23 x 15 c

Japanese Rural Society

xiv, 221 hal.: 21 cm; Inde

Correspondences regarding UBC Library as the Canadian depository library for Japanese Government Publications (1957-1958)

Eight letters among the University of British Columbia, the Canadian Embassy, the National Library of Canada, the Canadian Library Association and the National Diet Library of Japan are listed. All are about designating the University of British Columbia as the Canadian depository library for Japanese Government Publications.Library, UBCNon UBCUnreviewedOthe

Sociologists and "the Japanese model": a passing enthusiasm?

This article critiques the construction of `the Japanese model' of employment relations by sociologists in English language sociological research monographs, organization textbooks and introductory general textbooks. It demonstrates how marked differences emerged across the different genres and relates them to the different purposes of researchers and textbook writers.The article examines three particular puzzles. First, why did general textbooks adopt `the Japanese model' in the 1990s when media commentaries were announcing the demise of the Japanese model in Japan? Second, why did the 1990s textbooks use 1980s organization textbooks rather than research monographs for their sources? Third, why are general textbooks ready to distance themselves from the model in 2006 when researchers confirm continuing vitality in the Japanese model in large Japanese companies? Answering these questions reveals how sociological knowledge of Japanese employment has been generated, disseminated and used in research, teaching and policy debates