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Abstract：
UNASSIGNED: It has been reported that high blood pressure (HBP) and triglyceride (TG) are considered risk factors in immunoglobulin A nephropathy (IgAN). This study aimed to explore the causalities between HBP and TG, and IgAN on the basis of Mendelian randomization (MR) analysis.
UNASSIGNED: Firstly, the genome-wide association study (GWAS) summary data of IgAN (GCST90018866) and two exposure factors, TG (ukb-d-30870_raw) and HBP (ukb-a-437), were sourced from the GWAS Catalog and Integrative Epidemiology Unit (IEU) OpenGWAS databases, respectively. In this study, five methods were utilized to perform MR analysis after picking out single nucleotide polymorphisms (SNPs) as instrumental variables, including MR-Egger, weighted median, simple mode, weighted mode, and inverse variance weighted (IVW), followed by the sensitivity analysis containing the heterogeneity, horizontal pleiotropy test and leave-one-out (LOO) analysis. Finally, the enrichment analysis and interaction network construction of genes corresponding to SNPs of HBP and TG were performed.
UNASSIGNED: The univariate MR results revealed that HBP and TG regarded as risk factors were causally related to IgAN [TG: p = 0.046, odds ratio (OR) = 1.065, 95% confidence interval (CI) = 1.001-1.133; HBP: p = 7.09 × 10-7, OR = 1.970, 95% CI = 1.507-2.575] based on random-effect IVM method, of which TG had a weaker impact. The reliability of these univariate MR results was certified by the sensitivity analysis, in which there was no horizontal pleiotropy and exaggerated influence of each SNP. Furthermore, HBP was markedly causally related to IgAN (p = 0.000512) with the help of multivariate MR analysis, rather than TG (p = 0.332). Therefore, when HBP and TG occur simultaneously, HBP is a direct influencing factor on IgAN. Ultimately, a total of 208 and 153 genes separately corresponding to SNPs of TG and HBP were included in enrichment analysis, and thereinto, genes relevant to TG were mainly enriched in lipid homeostasis and cholesterol metabolism, while genes concerned with HBP played their roles in regulation of cell growth, aldosterone synthesis and secretion and so forth.
UNASSIGNED: TG and HBP as risk factors were causally connected with IgAN, of which HBP was strongly related to the onset of IgAN, providing more reliable evidence for further exploring the relationship between TG and HBP and IgAN.
UNASSIGNED: Firstly, the genome-wide association study (GWAS) summary data of IgAN (GCST90018866) and two exposure factors, TG (ukb-d-30870_raw) and HBP (ukb-a-437), were sourced from the GWAS Catalog and Integrative Epidemiology Unit (IEU) OpenGWAS databases, respectively. In this study, five methods were utilized to perform MR analysis after picking out single nucleotide polymorphisms (SNPs) as instrumental variables, including MR-Egger, weighted median, simple mode, weighted mode, and inverse variance weighted (IVW), followed by the sensitivity analysis containing the heterogeneity, horizontal pleiotropy test and leave-one-out (LOO) analysis. Finally, the enrichment analysis and interaction network construction of genes corresponding to SNPs of HBP and TG were performed.
UNASSIGNED: The univariate MR results revealed that HBP and TG regarded as risk factors were causally related to IgAN [TG: p = 0.046, odds ratio (OR) = 1.065, 95% confidence interval (CI) = 1.001-1.133; HBP: p = 7.09 × 10-7, OR = 1.970, 95% CI = 1.507-2.575] based on random-effect IVM method, of which TG had a weaker impact. The reliability of these univariate MR results was certified by the sensitivity analysis, in which there was no horizontal pleiotropy and exaggerated influence of each SNP. Furthermore, HBP was markedly causally related to IgAN (p = 0.000512) with the help of multivariate MR analysis, rather than TG (p = 0.332). Therefore, when HBP and TG occur simultaneously, HBP is a direct influencing factor on IgAN. Ultimately, a total of 208 and 153 genes separately corresponding to SNPs of TG and HBP were included in enrichment analysis, and thereinto, genes relevant to TG were mainly enriched in lipid homeostasis and cholesterol metabolism, while genes concerned with HBP played their roles in regulation of cell growth, aldosterone synthesis and secretion and so forth.
UNASSIGNED: TG and HBP as risk factors were causally connected with IgAN, of which HBP was strongly related to the onset of IgAN, providing more reliable evidence for further exploring the relationship between TG and HBP and IgAN.
摘要：
■据报道，高血压（HBP）和甘油三酸酯（TG）被认为是免疫球蛋白A肾病（IgAN）的危险因素。本研究旨在探讨HBP与TG之间的因果关系。和IgAN在孟德尔随机化（MR）分析的基础上。
■首先，IgAN（GCST90018866）的全基因组关联研究（GWAS）汇总数据和两个暴露因素，TG(UCB-D-30870_raw)和HBP(UCB-A-437)，来自GWAS目录和综合流行病学单位(IEU)OpenGWAS数据库，分别。在这项研究中,在挑选出单核苷酸多态性（SNP）作为工具变量后，使用五种方法进行MR分析，包括MR-Egger,加权中位数，简单模式，加权模式，和逆方差加权(IVW)，其次是包含异质性的敏感性分析，水平多效性测试和留一法(LOO)分析。最后,对HBP和TG的SNPs对应基因进行富集分析和互作网络构建。
■单变量MR结果显示，作为危险因素的HBP和TG与IgAN有因果关系[TG：p=0.046，比值比（OR）=1.065，95％置信区间（CI）=1.001-1.133；HBP：p=7.09×10-7，OR=1.970，95％CI=1.507-2.75]。其中TG的影响较弱。这些单变量MR结果的可靠性通过灵敏度分析得到了证明，其中没有水平多效性和每个SNP的夸大影响。此外，在多变量MR分析的帮助下，HBP与IgAN有明显的因果关系（p=0.000512），而不是TG（p=0.332）。因此,当HBP和TG同时发生时，HBP是IgAN的直接影响因子。最终,分别对应于TG和HBP的SNP的208和153个基因被包括在富集分析中,其中，与TG相关的基因主要富含脂质稳态和胆固醇代谢，而与HBP相关的基因在调节细胞生长中发挥作用，醛固酮的合成和分泌等等。
■TG和HBP作为危险因素与IgAN有因果关系，其中HBP与IgAN的发病密切相关，为进一步探讨TG和HBP与IgAN的关系提供更可靠的证据。
■首先，IgAN（GCST90018866）的全基因组关联研究（GWAS）汇总数据和两个暴露因素，TG(UCB-D-30870_raw)和HBP(UCB-A-437)，来自GWAS目录和综合流行病学单位(IEU)OpenGWAS数据库，分别。在这项研究中,在挑选出单核苷酸多态性（SNP）作为工具变量后，使用五种方法进行MR分析，包括MR-Egger,加权中位数，简单模式，加权模式，和逆方差加权(IVW)，其次是包含异质性的敏感性分析，水平多效性测试和留一法(LOO)分析。最后,对HBP和TG的SNPs对应基因进行富集分析和互作网络构建。
■单变量MR结果显示，作为危险因素的HBP和TG与IgAN有因果关系[TG：p=0.046，比值比（OR）=1.065，95％置信区间（CI）=1.001-1.133；HBP：p=7.09×10-7，OR=1.970，95％CI=1.507-2.75]。其中TG的影响较弱。这些单变量MR结果的可靠性通过灵敏度分析得到了证明，其中没有水平多效性和每个SNP的夸大影响。此外，在多变量MR分析的帮助下，HBP与IgAN有明显的因果关系（p=0.000512），而不是TG（p=0.332）。因此,当HBP和TG同时发生时，HBP是IgAN的直接影响因子。最终,分别对应于TG和HBP的SNP的208和153个基因被包括在富集分析中,其中，与TG相关的基因主要富含脂质稳态和胆固醇代谢，而与HBP相关的基因在调节细胞生长中发挥作用，醛固酮的合成和分泌等等。
■TG和HBP作为危险因素与IgAN有因果关系，其中HBP与IgAN的发病密切相关，为进一步探讨TG和HBP与IgAN的关系提供更可靠的证据。
