■先前学者提出的肠-视网膜轴的概念主要集中在肠道菌群与视网膜疾病之间的关系上,很少有人进一步扩大肠道疾病与视网膜疾病的关系。为了进一步证实肠-视网膜轴的概念,我们使用孟德尔随机化(MR)分析了炎症性肠病(IBD)和糖尿病性视网膜病变(DR),并利用中介分析进一步探讨影响这种因果关系的潜在物质。
■在孟德尔随机化(MR)调查中,利用了全基因组关联研究(GWAS)的遗传变异汇总统计。IBD的GWAS数据(包括溃疡性结肠炎(UC),克罗恩病(CD),和IBD)非芬兰欧洲人(NFE)来自已发表的文章。相比之下,DR(包括DR和糖尿病性黄斑病变(DMP))的数据来自FinnGenR9.因果关系已经使用逆方差加权(IVW)进行了研究,MR-Egger,加权中位数和敏感性分析验证了结果的稳定性。此外,我们应用中介分析来研究循环炎症蛋白和血浆脂质是否起中介作用,并计算了其效果比。
■通过使用逆方差加权(IVW)方法和加权中位数方法发现了IBD与DR之间的因果关系。在前MR中,UC与DR风险降低显著相关(IVW:OR=0.874;95CI=0.835-0.916;P值=1.28E-08)(加权中位数:OR=0.893;95CI=0.837-0.954;P值=7.40E-04)。在反向MR中,结果表明,DR(IVW:OR=0.870;95CI=0.828-0.914;P值=2.79E-08)(加权中位数:OR=0.857;95CI=0.801-0.916;P值=6.40E-06)和DMP(IVW:OR=0.900;95CI=0.865-37;P值=3.34E-07)(加权CI=0.9E-0.841)降低风险。更重要的是,根据基因预测,DR与IBD风险较低相关(IVW:OR=0.922;95CI=0.873-0.972;P值=0.002)(加权中位数:OR=0.924;95CI=0.861-0.992;P值=0.029)。成纤维细胞生长因子21(FGF21),磷脂酰胆碱(PC),三酰甘油(TG)在这些关系中充当介质。
■我们的研究为研究IBD和DR之间的遗传关系中的肠-视网膜轴提供了新的见解和来源。我们发现了四种介质,以及更多有关肠道和视网膜疾病之间的关联,并为肠-视网膜轴理论提供了更多证据。
UNASSIGNED: The concept of the gut-retinal axis proposed by previous scholars primarily focused on the relationship between intestinal microbiota and retinal diseases, and few further expanded the relationship between intestinal diseases and retinal diseases. To further substantiate the concept of the gut-retinal axis, we analyzed inflammatory bowel disease (IBD) and diabetic retinopathy (DR) using Mendelian randomization (MR), and use mediation analysis to further explore the potential substances that influence this causal relationship.
UNASSIGNED: The genome-wide association study\'s (GWAS) summary statistics for genetic variations were utilized in a Mendelian randomization (MR) investigation. GWAS data on IBD (including ulcerative colitis (UC), Crohn\'s disease (CD), and IBD) for non-Finnish Europeans (NFE) were sourced from published articles. In contrast, data on DR (including DR and diabetic maculopathy (DMP)) were obtained from FinnGen R9. The causal relationship has been investigated using inverse variance weighted (IVW), MR-Egger, and weighted median and sensitivity analysis was applied to verify the stability of the results. In addition, we applied mediation analysis to investigate whether circulating inflammatory proteins and plasma lipids played a mediating role, and calculated its effect ratio.
UNASSIGNED: The causal relationship between IBD and DR was discovered by employing the inverse variance weighted (IVW) method and weighted median method. In forward MR, UC was significantly associated with lower risk of DR (IVW: OR=0.874; 95%CI= 0.835-0.916; P value= 1.28E-08) (Weighted median: OR=0.893; 95%CI= 0.837-0.954; P value= 7.40E-04). In reverse MR, it was shown that DR (IVW: OR=0.870; 95%CI= 0.828-0.914; P value= 2.79E-08)(Weighted median: OR=0.857; 95%CI= 0.801-0.916; P value= 6.40E-06) and DMP (IVW: OR=0.900; 95%CI= 0.865-0.937; P value= 3.34E-07)(Weighted median: OR=0.882; 95%CI= 0.841-0.924; P value= 1.82E-07) could reduce the risk of CD. What\'s more, DR is associated with a lower risk of IBD according to genetic prediction (IVW: OR=0.922; 95%CI= 0.873-0.972; P value= 0.002) (Weighted median: OR=0.924; 95%CI= 0.861-0.992; P value= 0.029). Fibroblast growth factor 21 (FGF21), phosphatidylcholine (PC), and triacylglycerol (TG) serve as mediators in these relationships.
UNASSIGNED: Our research offers novel insights and sources for investigating the gut-retina axis in the genetic relationship between IBD and DR. We discover four mediators and more about the association between the intestine and retinal disorders and provide more evidence for the gut-retinal axis theory.