Association Between Glycemic Traits and Primary Open-Angle Glaucoma: A Mendelian Randomization Study in the Japanese Population
Association Between Glycemic Traits and Primary Open-Angle Glaucoma: A Mendelian Randomization Study in the Japanese Population
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DOI：
10.1016/j.ajo.2022.09.004
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发表时间：
2022-11-05
影响因子：
4.2
通讯作者：
Iwasaki, Motoki
中科院分区：
文献类型：
--
作者：
Hanyuda, Akiko;Goto, Atsushi;Iwasaki, Motoki
目的：荟萃分析表明葡萄糖代谢异常与原发性开角型青光眼 (POAG) 之间存在关系；然而，它们之间的因果关系仍然存在争议。因此，我们进行了孟德尔随机化 (MR) 研究，以评估基因预测的血糖特征与 POAG 风险之间的因果关系。中心点设计：两个样本 MR 设计。中心点方法：我们检查了与 POAG 相关的空腹血糖、血红蛋白 A1c (HbA1c) 和空腹 C 肽的基因预测测量值。对于单核苷酸多态性 (SNP) 暴露分析，我们荟萃分析了空腹血糖水平（n = 17,289；SNP 个数 = 34）、HbA1c（n = 52,802；SNP 个数 = 43）和空腹 C 肽水平（n = 1666；SNP 个数 = 17) 来自日本遗传流行病学研究联盟。我们使用日本 BioBank 项目的汇总统计数据（n = 3980 个 POAG 病例和 18,815 个对照）来进行 SNP 结果关联。中心点结果：我们观察到基因预测的 HbA1c 和空腹 C 肽与 POAG 没有关联。 HbA1c（每 1% 增量）的 MR 逆方差加权 (IVW) 比值比 (OR) 为 1.44（95% 置信区间 [CI]，0.78-2.65；P = .25），空腹 C 肽（每 2 倍增量）为 0.92（95% CI，0.56-1.53；P = .76）。根据 MR IVW 分析，观察到空腹血糖（每 10 mg/dL 增量）与 POAG 之间存在显着相关性（OR = 1.48 [95% CI，1.10-1.79，P = .009]）；然而，包括 MR-Egger 和加权中值方法在内的敏感性分析并不支持这种关联 ( P > .10)。中心点结论：我们没有观察到强有力的证据来支持日本人群中基因预测的血糖特征与 POAG 之间的关联。 （美国眼科杂志 2023；245：193-201。(c) 2022 Else-vier Inc. 保留所有权利。）
PURPOSE: A meta-analysis suggests a relationship be-tween abnormal glucose metabolism and primary open -angle glaucoma (POAG); however, the causal associa-tion between them remains controversial. We therefore conducted a Mendelian randomization (MR) study to as - sess the causal association between genetically predicted glycemic traits and the risk of POAG.center dot DESIGN: Two-sample MR design.center dot METHODS: We examined the genetically predicted mea-sures of fasting glucose, hemoglobin A1c (HbA1c), and fasting C-peptide, in relation to POAG. For the single nucleotide polymorphism (SNP) -exposure analyses, we meta-analyzed the study-level genome-wide associations of fasting glucose levels (n = 17,289; n of SNPs = 34), HbA1c (n = 52,802; n of SNPs = 43), and fasting C-peptide levels (n = 1666; n of SNPs = 17) from the Japanese Consortium of Genetic Epidemiology studies. We used summary statistics from the BioBank Japan projects (n = 3980 POAG cases and 18,815 controls) for the SNP -outcome association. center dot RESULTS: We observed no association of genetically predicted HbA1c and fasting C-peptide with POAG. The MR inverse-variance -weighted (IVW) odds ratios (ORs) were 1.44 (95% confidence interval [CI], 0.78-2.65; P = .25) for HbA1c (per 1% increment) and 0.92 (95% CI, 0.56-1.53; P = .76) for fasting C-peptide (per 2-fold increment). A significant association between fast-ing glucose (per 10 mg/dL-increment) and POAG was observed according to the MR IVW analysis (OR = 1.48 [95% CI, 1.10-1.79, P = .009]); however, sensitiv-ity analyses, including MR -Egger and weighted-median methods, did not support this association ( P > .10).center dot CONCLUSIONS: We did not observe strong evidence to support the association between genetically predicted glycemic traits and POAG in the Japanese population. (Am J Ophthalmol 2023;245: 193-201. (c) 2022 Else-vier Inc. All rights reserved.)