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| 2. |
- Konishi, Shoko, et al.
(author)
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Pollinosis and all-cause mortality among middle-aged and elderly Japanese : a population-based cohort study
- 2016
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 46:8, s. 1083-1089
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Journal article (peer-reviewed)abstract
- BACKGROUND: Having an allergic disease may have health implications beyond those more commonly associated with allergy given that previous epidemiological studies have suggested that both atopy and allergy are linked to mortality. More viable immune functioning among the elderly, as indicated by the presence of an allergic disease might therefore be associated with differences in all-cause mortality.OBJECTIVE: Using data from a Japanese cohort, this study examined whether having pollinosis (a form of allergic rhinitis) in a follow-up survey could predict all-cause and cause-specific mortality.METHODS: Data came from the Komo-Ise cohort, which at its 1993 baseline recruited residents aged 40-69 years old from two areas in Gunma prefecture, Japan. The current study used information on pollinosis that was obtained from the follow-up survey in 2000. Mortality and migration data were obtained throughout the follow-up period up to December 2008. Proportional hazard models were used to examine the relation between pollinosis and mortality.RESULTS: At the 2000 follow-up survey, 12% (1 088 out of 8 796) of respondents reported that they had pollinosis symptoms in the past 12 months. During the 76 186 person-years of follow-up, 748 died from all-causes. Among these there were 37 external, 208 cardiovascular, 74 respiratory, and 329 neoplasm deaths. After adjusting for potential confounders, pollinosis was associated with significantly lower all-cause (hazard ratio 0.57 [95% confidence interval = 0.38 to 0.87]) and neoplasms mortality (hazard ratio 0.48 [95% confidence interval = 0.26 to 0.92]).CONCLUSIONS AND CLINICAL RELEVANCE: Having an allergic disease (pollinosis) at an older age may be indicative of more viable immune functioning and be protective against certain causes of death. Further research is needed to determine the possible mechanisms underlying the association between pollinosis and mortality.
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| 3. |
- Namkoong, H, et al.
(author)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Journal article (peer-reviewed)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.
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| 4. |
- Ng, Chris Fook Sheng, et al.
(author)
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Ambient air pollution and suicide in Tokyo, 2001-2011
- 2016
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In: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 201, s. 194-202
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Journal article (peer-reviewed)abstract
- Background: Some evidence suggests an association may exist between the level of air pollution and suicide mortality. However, this relation has been little studied to date. The current study examined the association in Tokyo, Japan. Methods: Suicide mortality data for Tokyo for the 11-year period 2001-2011 were obtained together with data on four air pollutants: fine particulate matter (PM2.5), suspended particulate matter (SPM), sulphur dioxide (SO2) and nitrogen dioxide (NO2). A time-stratified case-crossover study design was used to examine the daily association between the level of air pollution and suicide mortality. Results: During the study period there were 29,939 suicide deaths. In stratified analyses an interquartile range (IQR) increase in the same-day concentration of NO2 was linked to increased suicide mortality among those aged under 30 (percentage change: 6.73%, 95% Cl: 0.69-13.12%). An IQR increase in PM25 and SO2 was associated with a 10.55% (95% Cl: 2.05-19.75%) and 11.47% (95% Cl: 3.60-19.93%) increase, respectively, in suicide mortality among widowed individuals for mean exposure on the first four days (average lags 0-3). Positive associations were observed for the air pollutants in the summer although associations were reversed in autumn. Limitations: We relied on monitoring data to approximate individual exposure to air pollutants. Conclusions: Higher levels of air pollution are associated with increased suicide mortality in some population subgroups in Tokyo. Further research is needed to elucidate the mechanisms linking air pollutants and suicide in this setting.
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| 5. |
- Wang, QBS, et al.
(author)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Journal article (peer-reviewed)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.
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