PDF(Pubmed)
Abstract：
Traditional observational research has revealed an association between severe COVID-19 and chronic kidney disease (CKD). It is unclear whether there is a causative connection between them. Our goal was to determine whether genetically predicted CKD is associated with the risk of critical COVID-19. We aimed to investigate potential underlying genetic mechanisms that could explain this relationship, paving the way for personalized risk assessment and targeted interventions to mitigate the effects of COVID-19 on individuals with CKD. Using combined data from a GWAS on European ancestry and CKD (n = 117,165) and critical COVID-19 (n = 1,059,456), bidirectional Mendelian randomization analysis was performed. Four single nucleotide polymorphisms (SNPs) were chosen from the genome as CKD instrumental variables (IVs). In addition to MR‒Egger regression, weighted mode approaches, and weighted medians, we employed the inverse-variance weighted estimate as our primary analytical method. A significant association of CKD with critical COVID-19 (OR = 1.28, 95% confidence interval [CI]: 1.04-1.58, p = 0.01811) was found. However, using 6 genome-wide significant SNPs as IVs for critical COVID-19, we could not discover a meaningful correlation between severe COVID-19 and CKD (OR = 1.03, 95% CI: 0.96-1.10, p = 0.3947). We found evidence to support a causal relationship between CKD and severe COVID-19 in European population. This underscores the need for comprehensive monitoring and specialized care strategies for individuals with CKD to mitigate the heightened risk and severity of COVID-19 complications.
摘要：
传统的观察性研究表明，严重的COVID-19与慢性肾脏疾病（CKD）之间存在关联。目前尚不清楚它们之间是否存在因果关系。我们的目标是确定基因预测的CKD是否与关键COVID-19的风险相关。我们的目的是研究解释这种关系的潜在潜在遗传机制，为个性化风险评估和针对性干预措施铺平道路，以减轻COVID-19对CKD患者的影响。使用来自GWAS的欧洲血统和CKD（n=117,165）和关键COVID-19（n=1,059,456）的组合数据，我们进行了双向孟德尔随机化分析.从基因组中选择四种单核苷酸多态性(SNP)作为CKD工具变量(IVs)。除了MR-Egger回归，加权模式方法，和加权中位数，我们采用逆方差加权估计作为我们的主要分析方法。发现CKD与临界COVID-19显著相关(OR=1.28，95%置信区间[CI]：1.04-1.58，p=0.01811)。然而,使用6个全基因组显著SNP作为关键COVID-19的IVs，我们无法发现严重COVID-19与CKD之间存在有意义的相关性(OR=1.03，95%CI：0.96-1.10，p=0.3947)。我们发现证据支持欧洲人群中CKD与严重COVID-19之间的因果关系。这凸显了对CKD患者进行全面监测和专门护理策略的必要性，以减轻COVID-19并发症的高风险和严重程度。
