ABSTRACT

Observational studies have been conducted to investigate the correlation between adiponectin and diabetic retinopathy (DR), but no consistent relationship has been established. In this study, we employed an integrative analysis that combined Mendelian randomization (MR) and bioinformatics analyses to comprehensively explore the association between DR and adiponectin, aiming to provide a unified answer of their relationship. Using the inverse-variance weighted (IVW) method, the odd ratio (OR) of developing DR per 1 mg/dL increment in genetically predicted log-transformed adiponectin concentration was estimated to be 0.949 (P = 0.557). Other robust MR methods produced consistent results, confirming the absence of a causal effect of adiponectin on DR. Additionally, the expression levels of the six adiponectin-related genes showed no significant differences among normal controls, individuals with diabetes but without DR, and those with DR Furthermore, the biological pathways enriched by these genes were not strongly relevant to DR. At both the individual gene and pathway levels, there were no overlaps between the adiponectin-related genes and the differentially expressed genes, indicating a lack of association between adiponectin and DR based on gene expression profiles. In summary, the integrative analysis, which combined MR and bioinformatics data mining, yielded compelling evidence supporting the notion that adiponectin is not a risk factor for DR.

摘要

已经进行了观察性研究来调查脂联素与糖尿病视网膜病变（DR）之间的相关性，但尚未建立一致的关系。在本研究中，我们采用孟德尔随机化（MR）和生物信息学分析相结合的综合分析方法，全面探讨DR与脂联素之间的关联，旨在为两者的关系提供统一的答案。使用逆方差加权 (IVW) 方法，基因预测的对数转换脂联素浓度每增加 1 mg/dL，发生 DR 的奇数比 (OR) 估计为 0.949 ( P = 0.557 )  。其他稳健的 MR 方法产生了一致的结果，证实脂联素对 DR 不存在因果影响。此外，6种脂联素相关基因的表达水平在正常对照、患有糖尿病但无DR的个体和患有DR的个体之间没有显示出显着差异。此外，这些基因富集的生物学途径与DR没有很强的相关性。在个体基因和通路水平上，脂联素相关基因和差异表达基因之间没有重叠，表明基于基因表达谱，脂联素和DR之间缺乏关联。总之，结合 MR 和生物信息学数据挖掘的综合分析产生了令人信服的证据，支持脂联素不是 DR 风险因素的观点。