The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Neutron diffraction study on manganese telluride

A neutron diffraction study of manganese telluride has been made using powder specimen. The specimen has been carefully checked by high temperature X-ray analysis and has been proved to be free from MnO and MnTe2 which are apt to contaminate the specimen. This investigation has shown that the magnetic structure of MnTe consists of ferromagnetic sheets in c-planes which are coupled antiferromagnetically along the c-axis. The d irection of spins lies within the ferromagnetic sheet. The magnetic form factor of Mn ions in MnTe has been found to be very close to the experimental values obtained by Corliss and others. The most probable value of the spin quantum number is obtained by neutron diffraction data as 4.6/2 and by the measurement of the magnetic susceptibility as 5.05/2. It implies that the maganese ion in MnTe has five unpaired electrons.L'étude en diffraction neutronique du tellurure de manganèse, a été faite sur une poudre. L'échantillon soigneusement analysé par rayons X à haute température a été prouvé être exempt de traces de MnO et de MnTe2 qui peuvent contaminer l'échantillon. L'etude a montré que la structure magnétique de MnTe consistait en plans c, ferromagnétiques couplés antiferromagnétiquement suivant l'axe c. La direction des spins est dans le plan c. Le facteur de forme magnétique des ions Mn dans MnTe a été trouvé très proche des valeurs expérimentales déjà données par Corliss et al. La valeur la plus probable du nombre quantique de spin d'après les résultats de la diffraction est 4,6/2 et, d'après les mesures de susceptibilité magnétique 5,05/2. Ceci implique que l'ion manganèse dans MnTe a 5 électrons non appariés

Photoemission study of itinerant ferromagnet Cr1-δ Te

The electronic structures of the itinerant ferromagnets Cr1-δTe (δ=0.05, 0.25, and 0.375) have been studied by photoemission spectroscopy. The valence-band spectra are compared with the density of states given by band-structure calculations. In spite of the itinerant nature of the d electrons, disagreement between the photoemission spectra and the band-structure calculations exists in the magnitude of the d-band exchange splitting and the spectral weight at the Fermi level and 2-4 eV below it: The occupied d band for δ=0.05 is shifted away from the Fermi level; the observed spectral weight at the Fermi level is significantly suppressed compared with the band-structure calculations for δ=0.05 and 0.375, where the nominal d-electron numbers are close to integers 4 and 3, respectively. Configuration-interaction cluster-model calculations have been made for δ=0.05 and 0.375 to explain the spectral weight distribution in the high-binding-energy (2-4 eV) region in terms of electron-correlation effects. The d-d on-site Coulomb energy is estimated to be significant, U∼2 eV, and nearly equal to or smaller than the charge-transfer energy Δ∼2-3 eV