Causal association between cystatin C and diabetic retinopathy: A two-sample Mendelian randomization study

IF 3.1 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes Investigation Pub Date : 2024-08-12 DOI:10.1111/jdi.14273

Yimeng Ruan, Ping Zhang, Xiangzhe Li, Xinru Jia, Dongwei Yao

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引用次数: 0

Abstract

Objective

To explore the causal relationship between cystatin C levels and different stages of diabetic retinopathy through Mendelian randomization (MR).

Methods

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.

Results

Based on the IVW method, we observed a causal relationship between cystatin C and diabetic retinopathy [odds ratio (OR)_{random effect} = 1.137, 95% confidence interval (CI): 1.035–1.250]/PDR (OR_{random effect} = 1.123, 95%CI: 1.004–1.255)/SNPBDR (OR_{fixed effect} = 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.

Conclusions

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.

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胱抑素 C 与糖尿病视网膜病变之间的因果关系：双样本孟德尔随机研究

目的通过孟德尔随机法（MR）探讨胱抑素C水平与糖尿病视网膜病变不同阶段之间的因果关系：MRC 综合流行病学组提供了与胱抑素 C（暴露）相关的全基因组关联研究（GWAS）数据。结果[DR、增殖性糖尿病视网膜病变（PDR）、严重非增殖性背景糖尿病视网膜病变（SNPBDR）]的全基因组关联研究数据来自芬兰基因组研究所。采用反方差加权（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效应：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[几率比（OR）随机效应 = 1.137，95% 置信区间（CI）：1.035-1.250]/PDR（OR 随机效应 = 1.123，95%CI：1.004-1.255）/SNPBDR（OR 固定效应 = 2.002，95%CI：1.343-2.986）。通过 cML-MA 方法得出了一致的结果。Cochran's Q 检验表明，胱抑素 C 水平和工具变量分别与糖尿病视网膜病变和增殖性糖尿病视网膜病变存在异质性。使用 MR-PRESSO 和径向 MR 对异常值进行调整后发现，胱抑素 C 水平与糖尿病视网膜病变之间的相关性仍具有统计学意义。反向 MR 分析表明，与基因相关的 SNPBDR 可能会影响胱抑素 C 水平。在多变量磁共振分析中，有迹象表明胱抑素C与DR/PDR/SNPBDR风险之间存在因果关系，并对混杂因素进行了调整：本研究利用孟德尔随机分析法确定了胱抑素 C 与糖尿病视网膜病变之间的因果关系，揭示了胱抑素 C 对糖尿病视网膜病变风险的影响，从而为糖尿病视网膜病变的临床干预提供了新的证据。

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来源期刊

Journal of Diabetes Investigation ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

9.40%

发文量

218

审稿时长

6-12 weeks

期刊介绍： Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).