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Proteome-wide Mende...
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Yoshiji, SatoshiMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;Kyoto Univ, Grad Sch Med, Kyoto McGill Int Collaborat Program Genom Med, Kyoto, Japan.;Japan Soc Promot Sci, Tokyo, Japan.
(author)
Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity
- Article/chapterEnglish2023
Publisher, publication year, extent ...
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2023-02-20
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Springer Nature,2023
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-502163
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-502163URI
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https://doi.org/10.1038/s42255-023-00742-wDOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:152002535URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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How obesity contributes to COVID-19 severity is not fully understood. In this study, Yoshiji et al. found that the plasma protein nephronectin partially mediates the effect of obesity on the risk of COVID-19 severity using a two-step Mendelian randomization approach and omics analyses. Obesity is a major risk factor for Coronavirus disease (COVID-19) severity; however, the mechanisms underlying this relationship are not fully understood. As obesity influences the plasma proteome, we sought to identify circulating proteins mediating the effects of obesity on COVID-19 severity in humans. Here, we screened 4,907 plasma proteins to identify proteins influenced by body mass index using Mendelian randomization. This yielded 1,216 proteins, whose effect on COVID-19 severity was assessed, again using Mendelian randomization. We found that an s.d. increase in nephronectin (NPNT) was associated with increased odds of critically ill COVID-19 (OR = 1.71, P = 1.63 x 10(-10)). The effect was driven by an NPNT splice isoform. Mediation analyses supported NPNT as a mediator. In single-cell RNA-sequencing, NPNT was expressed in alveolar cells and fibroblasts of the lung in individuals who died of COVID-19. Finally, decreasing body fat mass and increasing fat-free mass were found to lower NPNT levels. These findings provide actionable insights into how obesity influences COVID-19 severity.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Butler-Laporte, GuillaumeMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
(author)
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Lu, TianyuanMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Quantitat Life Sci Program, Montreal, PQ, Canada.;5 Prime Sci, Montreal, PQ, Canada.
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Willett, Julian Daniel SundayMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Quantitat Life Sci Program, Montreal, PQ, Canada.
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Su, Chen-YangMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Comp Sci, Montreal, PQ, Canada.
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Nakanishi, TomokoMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;Kyoto Univ, Grad Sch Med, Kyoto McGill Int Collaborat Program Genom Med, Kyoto, Japan.;Japan Soc Promot Sci, Tokyo, Japan.
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Morrison, David R.McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Chen, YihengMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
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Liang, KevinMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Quantitat Life Sci Program, Montreal, PQ, Canada.
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Hultström, Michael,1978-Uppsala universitet,Integrativ Fysiologi,Anestesiologi och intensivvård,McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.(Swepub:uu)mihul498
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Ilboudo, YannMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Afrasiabi, ZamanMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Lan, ShanshanMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Duggan, NaomiMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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DeLuca, ChantalMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Vaezi, MitraMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Tselios, ChrisMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Xue, XiaoqingMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Bouab, MeriemMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Shi, FangyiMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Laurent, LaetitiaMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Münter, Hans MarkusMcGill Univ, McGill Genome Ctr, Montreal, PQ, Canada.
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Afilalo, MarcMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Jewish Gen Hosp, Dept Emergency Med, Montreal, PQ, Canada.
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Afilalo, JonathanMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.;McGill Univ, Jewish Gen Hosp, Div Cardiol, Montreal, PQ, Canada.
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Mooser, VincentMcGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, McGill Genome Ctr, Montreal, PQ, Canada.
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Timpson, Nicholas J.Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
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Zeberg, HugoKarolinska Institutet,Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Max Planck Inst Evolutionary Anthropol, Leipzig, Germany.
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Zhou, SiruiMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, McGill Genome Ctr, Montreal, PQ, Canada.
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Forgetta, VincenzoMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;5 Prime Sci, Montreal, PQ, Canada.
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Farjoun, YossiMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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Richards, J. BrentMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.;5 Prime Sci, Montreal, PQ, Canada.;Kings Coll London, Dept Twin Res, London, England.
(author)
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McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;Kyoto Univ, Grad Sch Med, Kyoto McGill Int Collaborat Program Genom Med, Kyoto, Japan.;Japan Soc Promot Sci, Tokyo, Japan.McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
(creator_code:org_t)
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In:Nature Metabolism: Springer Nature5, s. 248-2642522-5812
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Yoshiji, Satoshi
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Butler-Laporte, ...
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Lu, Tianyuan
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Willett, Julian ...
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Su, Chen-Yang
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Nakanishi, Tomok ...
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Morrison, David ...
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Chen, Yiheng
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Liang, Kevin
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Hultström, Micha ...
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Ilboudo, Yann
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Afrasiabi, Zaman
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Lan, Shanshan
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Duggan, Naomi
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DeLuca, Chantal
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Vaezi, Mitra
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Tselios, Chris
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Xue, Xiaoqing
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Bouab, Meriem
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Shi, Fangyi
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Laurent, Laetiti ...
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Münter, Hans Mar ...
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Afilalo, Marc
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Afilalo, Jonatha ...
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Mooser, Vincent
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Timpson, Nichola ...
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Zeberg, Hugo
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Zhou, Sirui
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Forgetta, Vincen ...
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Farjoun, Yossi
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Richards, J. Bre ...
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