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Sökning: onr:"swepub:oai:DiVA.org:uu-502163" > Proteome-wide Mende...

Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity

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.
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.
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.
Su, Chen-Yang (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Comp Sci, Montreal, PQ, Canada.
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.
Morrison, David R. (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Chen, Yiheng (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
Liang, Kevin (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Quantitat Life Sci Program, Montreal, PQ, Canada.
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.
Ilboudo, Yann (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Afrasiabi, Zaman (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Lan, Shanshan (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Duggan, Naomi (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
DeLuca, Chantal (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Vaezi, Mitra (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Tselios, Chris (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Xue, Xiaoqing (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Bouab, Meriem (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Shi, Fangyi (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Laurent, Laetitia (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
Münter, Hans Markus (författare)
McGill Univ, McGill Genome Ctr, Montreal, PQ, Canada.
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.
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.
Mooser, Vincent (författare)
McGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, McGill Genome Ctr, Montreal, PQ, Canada.
Timpson, Nicholas J. (författare)
Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
Zeberg, Hugo (författare)
Karolinska Institutet,Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Max Planck Inst Evolutionary Anthropol, Leipzig, Germany.
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.
Forgetta, Vincenzo (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;5 Prime Sci, Montreal, PQ, Canada.
Farjoun, Yossi (författare)
McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.
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.
Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 5, s. 248-264
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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.

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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