| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Namkoong, H, et al.
(författare)
-
DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
-
Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. 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.
|
|
| 6. |
|
|
| 7. |
- Wang, QBS, et al.
(författare)
-
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Yin, Y. Y., et al.
(författare)
-
Quantifying Water Scarcity in Northern China Within the Context of Climatic and Societal Changes and South-to-North Water Diversion
- 2020
-
Ingår i: Earths Future. - : American Geophysical Union (AGU). - 2328-4277. ; 8:8
-
Tidskriftsartikel (refereegranskat)abstract
- With the increasing pressure from population growth and economic development, northern China (NC) faces a grand challenge of water scarcity, which can be further exacerbated by climatic and societal changes. The South-to-North Water Diversion (SNWD) project is designed to mitigate the water scarcity in NC. However, few studies have quantified the impact of the SNWD on water scarcity within the context of climatic and societal changes and its potential effects on economic and agricultural food in the region. We used water supply stress index (WaSSI) to quantify water scarcity within the context of environmental change in NC and developed a method to estimate the economic and agricultural impacts of the SNWD. Focuses were put on alleviating the water supply shortage and economic and agricultural benefits for the water-receiving NC. We find that societal changes, especially economic growth, are the major contributors to water scarcity in NC during 2009-2099. To completely mitigate the water scarcity of NC, at least an additional water supply of 13 billion m(3)/year (comparable to the annual diversion water by SNWD Central Route) will be necessary. Although SNWD alone cannot provide the full solution to NC's water shortage in next few decades, it can significantly alleviate the water supply stress in NC (particularly Beijing), considerably increasing the agricultural production (more than 115 Tcal/year) and bringing economic benefits (more than 51 billion RMB/year) through supplying industrial and domestic water use. Additionally, the transfer project could have impacts on the ecological environment in the exporting regions.
|
|
