Proteome-wide Mendelian randomization implicates nephronectin as an actionable mediator of the effect of obesity on COVID-19 severity
書誌事項
- 公開日
- 2023-02-20
- 資源種別
- journal article
- 権利情報
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- https://www.springernature.com/gp/researchers/text-and-data-mining
- https://www.springernature.com/gp/researchers/text-and-data-mining
- DOI
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- 10.1038/s42255-023-00742-w
- 10.1101/2022.06.06.22275997
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title> <jats:p> Obesity is a major risk factor for COVID-19 severity; however, the mechanisms underlying this relationship are not fully understood. Since 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 (BMI) using Mendelian randomization (MR). This yielded 1,216 proteins, whose effect on COVID-19 severity was assessed, again using MR. We found that a standard deviation increase in nephronectin (NPNT) was associated with increased odds of critically ill COVID-19 (OR = 1.71, <jats:italic>P</jats:italic> = 1.63 × 10 <jats:sup>−10</jats:sup> ). The effect was driven by an NPNT splice isoform. Mediation analyses supported NPNT as a mediator. In single-cell RNA-sequencing, <jats:italic>NPNT</jats:italic> 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. </jats:p>
収録刊行物
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- Nature Metabolism
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Nature Metabolism 5 (2), 248-264, 2023-02-20
Springer Science and Business Media LLC
