Department of Ophthalmology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, China.
Ningbo XinShi Eye Hospital, Ningbo, Zhejiang Province, China.
J Diabetes Investig. 2024 Nov;15(11):1626-1636. doi: 10.1111/jdi.14273. Epub 2024 Aug 12.
To explore the causal relationship between cystatin C levels and different stages of diabetic retinopathy through Mendelian randomization (MR).
The MRC Integrative Epidemiology Unit provided the Genome-wide association studies (GWAS) data related to cystatin C (exposure). GWAS data for outcomes [DR, proliferative diabetic retinopathy (PDR), severe non-proliferative background diabetic retinopathy (SNPBDR)] were sourced from the FinnGen. Adopted Inverse Variance Weighting (IVW), MR-Egger regression MR-PRESSO, Weighted Median, Constrained Maximum Likelihood and Model Averaging (cML-MA), Weighted model, Radial MR, and MR-Lasso to estimate the causal relationship between cystatin C and diabetic retinopathy. We conducted multivariable MR analysis to evaluate the independent causal effects of cystatin C levels on diabetic retinopathy.
Based on the IVW method, we observed a causal relationship between cystatin C and diabetic retinopathy [odds ratio (OR) = 1.137, 95% confidence interval (CI): 1.035-1.250]/PDR (OR = 1.123, 95%CI: 1.004-1.255)/SNPBDR (OR = 2.002, 95%CI: 1.343-2.986). Consistent findings were obtained through the cML-MA method. Cochran's Q test suggested the presence of heterogeneity between the cystatin C level and instrumental variables in relation to diabetic retinopathy and proliferative diabetic retinopathy, respectively. After adjusting for outliers using MR-PRESSO and Radial MR, it was observed that the statistical significance of the association between cystatin C level and diabetic retinopathy persists. Reverse MR analysis indicated that genetically related SNPBDR may influence the cystatin C level. In multivariable MR analysis, there were indications suggesting a causal relationship of cystatin C with the risk of DR/PDR/SNPBDR adjusting for confounders.
This study utilizes Mendelian randomization analyses to establish a causal relationship between cystatin C and diabetic retinopathy, and reveals the impact of cystatin C on the risk of diabetic retinopathy, thus providing new evidence for clinical intervention of diabetic retinopathy.
通过孟德尔随机化（MR）研究胱抑素 C 水平与糖尿病视网膜病变不同阶段之间的因果关系。
MRC 综合流行病学单位提供了与胱抑素 C（暴露）相关的全基因组关联研究（GWAS）数据。结局[糖尿病性视网膜病变（DR）、增生性糖尿病性视网膜病变（PDR）、严重非增生性背景糖尿病性视网膜病变（SNPBDR）]的 GWAS 数据来源于 FinnGen。采用逆方差加权（IVW）、MR-Egger 回归 MR-PRESSO、加权中位数、约束最大似然和模型平均（cML-MA）、加权模型、径向 MR 和 MR-Lasso 来估计胱抑素 C 与糖尿病视网膜病变之间的因果关系。我们进行了多变量 MR 分析，以评估胱抑素 C 水平对糖尿病视网膜病变的独立因果影响。
根据 IVW 方法，我们观察到胱抑素 C 与糖尿病视网膜病变之间存在因果关系[比值比（OR）=1.137，95%置信区间（CI）：1.035-1.250]/PDR（OR=1.123，95%CI：1.004-1.255）/SNPBDR（OR=2.002，95%CI：1.343-2.986）。cML-MA 方法得到了一致的结果。Cochran's Q 检验表明，胱抑素 C 水平与与糖尿病视网膜病变和增生性糖尿病视网膜病变相关的工具变量之间存在异质性。使用 MR-PRESSO 和 Radial MR 排除异常值后，观察到胱抑素 C 水平与糖尿病视网膜病变之间的关联仍然具有统计学意义。反向 MR 分析表明，遗传相关的 SNPBDR 可能影响胱抑素 C 水平。在多变量 MR 分析中，调整混杂因素后，胱抑素 C 与 DR/PDR/SNPBDR 风险之间存在因果关系的迹象。
本研究利用孟德尔随机化分析确立了胱抑素 C 与糖尿病视网膜病变之间的因果关系，并揭示了胱抑素 C 对糖尿病视网膜病变风险的影响，为糖尿病视网膜病变的临床干预提供了新的证据。
