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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 ...

  • 2023-02-20
  • Springer Nature,2023
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-502163
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-502163URI
  • https://doi.org/10.1038/s42255-023-00742-wDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:152002535URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 ...)

  • Butler-Laporte, GuillaumeMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. (author)
  • 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. (author)
  • Willett, Julian Daniel SundayMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Quantitat Life Sci Program, Montreal, PQ, Canada. (author)
  • Su, Chen-YangMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Comp Sci, Montreal, PQ, Canada. (author)
  • 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. (author)
  • Morrison, David R.McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Chen, YihengMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ, Canada. (author)
  • Liang, KevinMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Quantitat Life Sci Program, Montreal, PQ, Canada. (author)
  • 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 (author)
  • Ilboudo, YannMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Afrasiabi, ZamanMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Lan, ShanshanMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Duggan, NaomiMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • DeLuca, ChantalMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Vaezi, MitraMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Tselios, ChrisMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Xue, XiaoqingMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Bouab, MeriemMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Shi, FangyiMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Laurent, LaetitiaMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • Münter, Hans MarkusMcGill Univ, McGill Genome Ctr, Montreal, PQ, Canada. (author)
  • Afilalo, MarcMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;McGill Univ, Jewish Gen Hosp, Dept Emergency Med, Montreal, PQ, Canada. (author)
  • 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. (author)
  • Mooser, VincentMcGill Univ, Dept Human Genet, Montreal, PQ, Canada.;McGill Univ, McGill Genome Ctr, Montreal, PQ, Canada. (author)
  • Timpson, Nicholas J.Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England. (author)
  • Zeberg, HugoKarolinska Institutet,Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Max Planck Inst Evolutionary Anthropol, Leipzig, Germany. (author)
  • 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. (author)
  • Forgetta, VincenzoMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada.;5 Prime Sci, Montreal, PQ, Canada. (author)
  • Farjoun, YossiMcGill Univ, Jewish Gen Hosp, Lady Davis Inst, Montreal, PQ, Canada. (author)
  • 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)
  • 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)

Related titles

  • In:Nature Metabolism: Springer Nature5, s. 248-2642522-5812

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