Huang Yu-Chuen, Chang Ya-Wen, Cheng Chun-Wen, Wu Chia-Ming, Liao Wen-Ling, Tsai Fuu-Jen
School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
Genetic Center, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan.
Genes (Basel). 2020 Dec 24;12(1):17. doi: 10.3390/genes12010017.
Adiponectin (APN) is suggested to be a potential biomarker for predicting diabetic retinopathy (DR) risk, but the association between APN and DR has been inconsistent in observational studies. We used a Mendelian randomization (MR) analysis to evaluate if circulating APN levels result in DR. We applied three different genetic risk scores (GRS): GRS combined all 47 single nucleotide polymorphisms (SNPs), which from a genome-wide association study (GWAS) database-catalog reach significance level; GRS comprised 16 GRS-SNPs with a rigorous threshold ( < 5.0 × 10 for GWAS), and GRS combined 5 SNPs significantly associated with APN level. The MR-inverse-variance weighted method analysis showed that for each 1-SD increase in genetically induced increase in plasma APN, the OR of having DR was β = 0.20 (95% CI: -0.46-0.85, = 0.553) for GRS, 0.61 (95% CI: 0.10-1.13, = 0.020) for GRS, and 0.57 (95% CI: -0.06 to 1.20, = 0.078) for GRS. Sensitivity analysis, including MR-egger regression and the weighted-median approach, did not provide evidence of the pleiotropic effect of IVs. Limited evidence for the causal role of APN in DR risk among Taiwanese diabetic patients was shown based on MR analysis in the present study.
脂联素(APN)被认为是预测糖尿病视网膜病变(DR)风险的潜在生物标志物,但在观察性研究中,APN与DR之间的关联并不一致。我们采用孟德尔随机化(MR)分析来评估循环APN水平是否会导致DR。我们应用了三种不同的遗传风险评分(GRS):GRS结合了来自全基因组关联研究(GWAS)数据库目录中达到显著水平的所有47个单核苷酸多态性(SNP);GRS由16个具有严格阈值(GWAS中<5.0×10)的GRS-SNP组成,GRS结合了5个与APN水平显著相关的SNP。MR逆方差加权法分析表明,对于基因诱导的血浆APN每增加1个标准差,GRS发生DR的OR为β = 0.20(95%CI:-0.46-0.85,P = 0.553),GRS为0.61(95%CI:0.10-1.13,P = 0.020),GRS为0.57(95%CI:-0.06至1.20,P = 0.078)。敏感性分析,包括MR-egger回归和加权中位数方法,未提供IVs多效性效应的证据。基于本研究中的MR分析,显示台湾糖尿病患者中APN在DR风险中的因果作用证据有限。