PDF(Pubmed)
Abstract：
BACKGROUND: Pressure ulcer (PU) is known to be associated with abnormalities of micronutrient status. However, to date, it is not clear whether a causal relationship exists between circulating levels of micronutrients and their supplementations and PU.
METHODS: A two-sample Mendelian randomization (MR) study was conducted using summary statistics from Genome-Wide Association Studies (GWAS). Genetic instrumental variables (IVs) for 13 micronutrients were identified from a GWAS of 67 582 participants, IVs for supplement zinc were acquired from 18 826 cases and 44 255 880 controls, and IVs for PU were obtained from 663 PUs and 207 482 controls. The MR analysis was conducted using the MR base platform. The main analysis method was inverse variance weighted (IVW) analysis, supplemented by MR Egger, Weighted median, Weighted mode, and Simple mode analyses. Heterogeneity was assessed using Cochran\'s Q statistic for MR-IVW and Rucker\'s Q statistic for MR-Egger. Pleiotropy was determined by the MR-Egger regression. Sensitivity analysis was conducted using the leave-one-out method, and publication bias was evaluated using funnel plots.
RESULTS: Genetically predicted lower circulating zinc levels were found to be causally linked to the development of PU (OR = 0.758, 95%CI 0.583-0.987, P = 0.040). However, there was no significant evidence of a causal relationship between supplemental zinc intake and PU development (P > 0.05). Additionally, no causal association was observed between the other circulating micronutrients and the occurrence of PU. Furthermore, there was no indication of horizontal pleiotropy or heterogeneity among genetic variants (P > 0.05), and the robustness of the findings was confirmed through leave-one-out tests and funnel plots.
CONCLUSIONS: Our findings indicate a potential causal association between circulating zinc levels and decreased risk of PU. However, zinc supplementation did not demonstrate a significant reduction in the risk of PU. Further research is warranted to elucidate the underlying mechanisms through which zinc influences the pathogenesis of PU and evaluate the efficacy of zinc supplementation in the prevention and management of PU.
METHODS: A two-sample Mendelian randomization (MR) study was conducted using summary statistics from Genome-Wide Association Studies (GWAS). Genetic instrumental variables (IVs) for 13 micronutrients were identified from a GWAS of 67 582 participants, IVs for supplement zinc were acquired from 18 826 cases and 44 255 880 controls, and IVs for PU were obtained from 663 PUs and 207 482 controls. The MR analysis was conducted using the MR base platform. The main analysis method was inverse variance weighted (IVW) analysis, supplemented by MR Egger, Weighted median, Weighted mode, and Simple mode analyses. Heterogeneity was assessed using Cochran\'s Q statistic for MR-IVW and Rucker\'s Q statistic for MR-Egger. Pleiotropy was determined by the MR-Egger regression. Sensitivity analysis was conducted using the leave-one-out method, and publication bias was evaluated using funnel plots.
RESULTS: Genetically predicted lower circulating zinc levels were found to be causally linked to the development of PU (OR = 0.758, 95%CI 0.583-0.987, P = 0.040). However, there was no significant evidence of a causal relationship between supplemental zinc intake and PU development (P > 0.05). Additionally, no causal association was observed between the other circulating micronutrients and the occurrence of PU. Furthermore, there was no indication of horizontal pleiotropy or heterogeneity among genetic variants (P > 0.05), and the robustness of the findings was confirmed through leave-one-out tests and funnel plots.
CONCLUSIONS: Our findings indicate a potential causal association between circulating zinc levels and decreased risk of PU. However, zinc supplementation did not demonstrate a significant reduction in the risk of PU. Further research is warranted to elucidate the underlying mechanisms through which zinc influences the pathogenesis of PU and evaluate the efficacy of zinc supplementation in the prevention and management of PU.
摘要：
背景：已知压力性溃疡（PU）与微量营养素状态异常有关。然而,到目前为止,目前尚不清楚微量营养素的循环水平及其补充剂和PU之间是否存在因果关系。
方法：使用全基因组关联研究（GWAS）的汇总统计进行了双样本孟德尔随机化（MR）研究。从67.582名参与者的GWAS中确定了13种微量营养素的遗传工具变量（IV），从18.826例和44.255.880例对照中获得补充锌的IVs，PU的IVs来自663个PU和207.482个对照。使用MR基础平台进行MR分析。主要的分析方法是方差加权逆(IVW)分析，由埃格先生补充，加权中位数，加权模式,和简单的模式分析。使用Cochran的Q统计量对MR-IVW进行评估，Rucker的Q统计量对MR-Egger进行评估。通过MR-Egger回归来确定多效性。敏感性分析采用留一法，使用漏斗图评估发表偏倚。
结果：基因预测的低循环锌水平与PU的发展有因果关系（OR=0.758，95CI0.583-0.987，P=0.040）。然而,补充锌摄入与PU发育之间没有显著的因果关系(P>0.05)。此外,在其他循环微量营养素与PU的发生之间未观察到因果关系。此外，遗传变异之间没有水平多效性或异质性的迹象（P>0.05），通过留一法检验和漏斗图证实了研究结果的稳健性。
结论：我们的研究结果表明循环锌水平与PU风险降低之间存在潜在的因果关系。然而,锌补充并未显示PU风险的显著降低.需要进一步的研究来阐明锌影响PU发病机理的潜在机制，并评估锌补充剂在PU预防和管理中的功效。
方法：使用全基因组关联研究（GWAS）的汇总统计进行了双样本孟德尔随机化（MR）研究。从67.582名参与者的GWAS中确定了13种微量营养素的遗传工具变量（IV），从18.826例和44.255.880例对照中获得补充锌的IVs，PU的IVs来自663个PU和207.482个对照。使用MR基础平台进行MR分析。主要的分析方法是方差加权逆(IVW)分析，由埃格先生补充，加权中位数，加权模式,和简单的模式分析。使用Cochran的Q统计量对MR-IVW进行评估，Rucker的Q统计量对MR-Egger进行评估。通过MR-Egger回归来确定多效性。敏感性分析采用留一法，使用漏斗图评估发表偏倚。
结果：基因预测的低循环锌水平与PU的发展有因果关系（OR=0.758，95CI0.583-0.987，P=0.040）。然而,补充锌摄入与PU发育之间没有显著的因果关系(P>0.05)。此外,在其他循环微量营养素与PU的发生之间未观察到因果关系。此外，遗传变异之间没有水平多效性或异质性的迹象（P>0.05），通过留一法检验和漏斗图证实了研究结果的稳健性。
结论：我们的研究结果表明循环锌水平与PU风险降低之间存在潜在的因果关系。然而,锌补充并未显示PU风险的显著降低.需要进一步的研究来阐明锌影响PU发病机理的潜在机制，并评估锌补充剂在PU预防和管理中的功效。
