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Proteome-wide Mende...
Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity
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- Yoshiji, Satoshi (författare)
- 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.
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- Butler-Laporte, Guillaume (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
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- Lu, Tianyuan (författare)
- McGill 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 Sunday (författare)
- McGill 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-Yang (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Comp Sci, Montreal, PQ, Canada.
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- Nakanishi, Tomoko (författare)
- 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.
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- Morrison, David R. (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Chen, Yiheng (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
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- Liang, Kevin (författare)
- McGill 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- (författare)
- 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.
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- Ilboudo, Yann (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Afrasiabi, Zaman (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Lan, Shanshan (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Duggan, Naomi (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- DeLuca, Chantal (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Vaezi, Mitra (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Tselios, Chris (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Xue, Xiaoqing (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Bouab, Meriem (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Shi, Fangyi (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Laurent, Laetitia (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Münter, Hans Markus (författare)
- McGill Univ, McGill Genome Ctr, Montreal, PQ, Canada.
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- Afilalo, Marc (författare)
- McGill 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, Jonathan (författare)
- McGill 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, Vincent (författare)
- McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, McGill Genome Ctr, Montreal, PQ, Canada.
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- Timpson, Nicholas J. (författare)
- Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
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- Zeberg, Hugo (författare)
- Karolinska Institutet,Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Max Planck Inst Evolutionary Anthropol, Leipzig, Germany.
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- Zhou, Sirui (författare)
- McGill 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, Vincenzo (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;5 Prime Sci, Montreal, PQ, Canada.
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- Farjoun, Yossi (författare)
- McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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- Richards, J. Brent (författare)
- McGill 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.
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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)
- 2023-02-20
- 2023
- Engelska.
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Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 5, s. 248-264
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
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- Av författaren/redakt...
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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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visa fler...
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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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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Hälsovetenskap
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och Folkhälsovetensk ...
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Nature Metabolis ...
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet