Gout is a prevalent manifestation of metabolic osteoarthritis induced by elevated blood uric acid levels. The purpose of this study was to investigate the mechanisms of gene expression regulation in gout disease and elucidate its pathogenesis. The study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and gout. We identified 17 association signals for gout at unique genetic loci, including four genes related by protein-protein interaction network (PPI) analysis: TRIM46, THBS3, MTX1, and KRTCAP2. Additionally, we discerned 22 methylation sites in relation to gout. The study also found that genes such as TRIM46, MAP3K11, KRTCAP2, and TM7SF2 could potentially elevate the risk of gout. Through a Mendelian randomization (MR) analysis, we identified three proteins causally associated with gout: ADH1B, BMP1, and HIST1H3A. According to our findings, gout is linked with the expression and function of particular genes and proteins. These genes and proteins have the potential to function as novel diagnostic and therapeutic targets for gout. These discoveries shed new light on the pathological mechanisms of gout and clear the way for future research on this condition. This study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and explored the gene expression regulation mechanisms of gout. This study used two-sample Mendelian randomization method to understand the causal relationship between proteins and gout. This study identified 17 genetic loci associated with gout, including four genes related by protein-protein interaction network (PPI) analysis: TRIM46, THBS3, MTX1 and KRTCAP2. This study also identified 22 methylation sites related to gout, and genes that may increase the risk of gout, such as TRIM46, MAP3K11, KRTCAP2 and TM7SF2. This study determined three proteins causally associated with gout by Mendelian randomization (MR) analysis: ADH1B, BMP1 and HIST1H3A.

中文翻译：

---

单细胞和全基因组孟德尔随机化确定了痛风的致病基因


痛风是由血尿酸水平升高引起的代谢性骨关节炎的普遍表现。本研究的目的是探讨痛风疾病的基因表达调控机制并阐明其发病机制。该研究整合痛风全基因组关联研究（GWAS）数据、单细胞转录组学（scRNA-seq）、表达数量性状基因座（eQTL）和甲基化数量性状基因座（mQTL）数据进行分析，并利用两样本孟德尔随机化研究，以了解蛋白质与痛风之间的因果关系。我们在独特的基因位点鉴定了 17 个痛风关联信号，包括通过蛋白质-蛋白质相互作用网络 (PPI) 分析相关的 4 个基因：TRIM46、THBS3、MTX1 和 KRTCAP2。此外，我们还发现了 22 个与痛风相关的甲基化位点。研究还发现 TRIM46、MAP3K11、KRTCAP2 和 TM7SF2 等基因可能会增加痛风的风险。通过孟德尔随机化 (MR) 分析，我们确定了三种与痛风因果相关的蛋白质：ADH1B、BMP1 和 HIST1H3A。根据我们的研究结果，痛风与特定基因和蛋白质的表达和功能有关。这些基因和蛋白质有可能成为痛风的新诊断和治疗靶点。这些发现为痛风的病理机制提供了新的线索，并为未来研究这一疾病扫清了道路。本研究整合痛风全基因组关联研究（GWAS）数据、单细胞转录组学（scRNA-seq）、表达数量性状位点（eQTL）和甲基化数量性状位点（mQTL）数据进行分析，探讨基因表达调控痛风的机制。 本研究采用两样本孟德尔随机化方法来了解蛋白质与痛风之间的因果关系。这项研究确定了 17 个与痛风相关的基因位点，其中包括通过蛋白质-蛋白质相互作用网络 (PPI) 分析相关的 4 个基因：TRIM46、THBS3、MTX1 和 KRTCAP2。这项研究还鉴定了22个与痛风相关的甲基化位点，以及可能增加痛风风险的基因，如TRIM46、MAP3K11、KRTCAP2和TM7SF2。这项研究通过孟德尔随机化 (MR) 分析确定了三种与痛风因果相关的蛋白质：ADH1B、BMP1 和 HIST1H3A。