Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Urolithiasis. 2024 Nov 30;53(1):2. doi: 10.1007/s00240-024-01667-z.
Kidney stones are a common urological condition caused by a complex interaction of genetic, metabolic, and environmental factors. Recent genomic research has shed light on the genetic basis of kidney stone susceptibility.This study aims to identify protein quantitative trait loci (pQTL) associated with kidney stone formation and explore their causal relationships using Mendelian randomization.We conducted two-sample Mendelian Randomization (MR) analyses utilizing Genome-Wide Association Study (GWAS) summary data to assess the causal impact of pQTL on kidney stone formation. Data sources included the UK Biobank dataset "ukb-b-8297" and an external validation dataset "ukb-b-13537". We employed inverse variance weighting (IVW) as the primary MR method, supplemented by sensitivity analyses such as MR-PRESSO, Leave-One-Out, and Cochran Q tests to validate the robustness of our findings.Our analyses identified significant associations between several pQTL and kidney stones. Key proteins such as CD27, CXCL9, and TNFRSF1A exhibited significant centrality in the protein-protein interaction (PPI) network, suggesting their critical roles in kidney stone pathogenesis. The KEGG pathway enrichment analysis revealed significant pathways, including cytokine-cytokine receptor interaction and osteoclast differentiation, highlighting the involvement of immune response and inflammatory processes in kidney stone formation.This study underscores the significance of pQTL in kidney stone research, identifying key proteins and pathways that may serve as biomarkers or therapeutic targets. The findings provide insights into the genetic and molecular mechanisms underlying kidney stone formation, offering potential avenues for future research and therapeutic interventions.
肾结石是一种常见的泌尿系统疾病，由遗传、代谢和环境因素的复杂相互作用引起。最近的基因组研究揭示了肾结石易感性的遗传基础。本研究旨在确定与肾结石形成相关的蛋白质数量性状基因座 (pQTL)，并使用孟德尔随机化方法探索其因果关系。我们进行了两样本孟德尔随机化 (MR) 分析，利用全基因组关联研究 (GWAS) 汇总数据来评估 pQTL 对肾结石形成的因果影响。数据来源包括英国生物库数据集“ukb-b-8297”和外部验证数据集“ukb-b-13537”。我们采用逆方差加权 (IVW) 作为主要的 MR 方法，并通过 MR-PRESSO、Leave-One-Out 和 Cochran Q 检验等敏感性分析来验证我们发现的稳健性。我们的分析确定了几个 pQTL 与肾结石之间存在显著关联。关键蛋白，如 CD27、CXCL9 和 TNFRSF1A，在蛋白质-蛋白质相互作用 (PPI) 网络中表现出显著的中心性，表明它们在肾结石发病机制中具有关键作用。KEGG 途径富集分析显示了显著的途径，包括细胞因子-细胞因子受体相互作用和破骨细胞分化，突出了免疫反应和炎症过程在肾结石形成中的参与。这项研究强调了 pQTL 在肾结石研究中的重要性，确定了可能作为生物标志物或治疗靶点的关键蛋白和途径。这些发现为肾结石形成的遗传和分子机制提供了深入了解，为未来的研究和治疗干预提供了潜在途径。
