Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China; National Clinical Research Center for Ocular Disease, Wenzhou, Zhejiang, China.
Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China; National Clinical Research Center for Ocular Disease, Wenzhou, Zhejiang, China; Opthalmology Department, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
Ophthalmology. 2022 Sep;129(9):1014-1021. doi: 10.1016/j.ophtha.2022.04.027. Epub 2022 May 10.
To explore whether there is a causal relationship between coffee consumption and primary open-angle glaucoma (POAG).
Two-sample Mendelian randomization (MR).
The single-nucleotide polymorphisms (SNPs) associated with coffee consumption (including phenotypes 1 and 2) were selected from a genome-wide association study (GWAS) involving 121 824 individuals of European descent. Coffee intake from the MRC-IEU UK Biobank was also used to identify instruments for coffee intake. Summary-level data for POAG were obtained from the largest publicly available meta-analyses involving 16 677 POAG cases and 199 580 controls of European descent.
The inverse variance-weighted (IVW) method was the main MR analysis, whereas weighted-median, weighted mode-based estimate (MBE), MR Pleiotropy RESidual Sum and Outlier (PRESSO) test, and MR-Egger regression were used for sensitivity analysis.
Diagnosis of POAG.
Three sets of instrumental variables were used to evaluate the causal association between coffee consumption and POAG risk. Results showed that genetically predicted higher coffee consumption phenotype 1 (cups/day) was significantly associated with higher risk of POAG (odds ratio [OR], 1.241; 95% confidence interval [CI], 1.041-1.480; P = 0.016). Genetically predicted higher coffee consumption phenotype 2 (high vs. no/low) was also significantly associated with higher risk of POAG (OR, 1.155; 95% CI, 1.038-1.284; P = 0.008, using the IVW method). Moreover, genetically predicted higher coffee intake from the MRC-IEU UK Biobank OpenGWAS was significantly associated with a higher risk of POAG (OR, 1.727; 95% CI, 1.230-2.425; P = 0.002, using the IVW method). Sensitivity analyses confirmed that the findings were robust to possible pleiotropy.
These findings provide the genetic evidence that higher coffee consumption is associated with a higher risk of POAG. Given that coffee is widely consumed, our findings provide new insights into potential strategies to prevent and manage POAG.
探讨咖啡摄入与原发性开角型青光眼（POAG）之间是否存在因果关系。
两样本孟德尔随机化（MR）。
与咖啡摄入相关的单核苷酸多态性（SNP）（包括表型 1 和 2）是从一项涉及 121824 名欧洲血统个体的全基因组关联研究（GWAS）中选择的。还使用 MRC-IEU 英国生物银行的咖啡摄入量来确定咖啡摄入量的工具。POAG 的汇总水平数据来自最大的公开可用荟萃分析，涉及 16677 例 POAG 病例和 199580 例欧洲血统对照。
逆方差加权（IVW）法是主要的 MR 分析，而加权中位数、加权模式估计（MBE）、MR 偏倚残留总和和异常值（PRESSO）检验以及 MR-Egger 回归用于敏感性分析。
POAG 的诊断。
使用三组工具变量来评估咖啡摄入与 POAG 风险之间的因果关系。结果表明，遗传预测的较高咖啡摄入表型 1（杯/天）与 POAG 风险增加显著相关（优势比[OR]，1.241；95%置信区间[CI]，1.041-1.480；P=0.016）。遗传预测的较高咖啡摄入表型 2（高 vs. 无/低）也与 POAG 风险增加显著相关（OR，1.155；95%CI，1.038-1.284；P=0.008，采用 IVW 法）。此外，遗传预测的 MRC-IEU 英国生物银行 OpenGWAS 中较高的咖啡摄入量与 POAG 风险增加显著相关（OR，1.727；95%CI，1.230-2.425；P=0.002，采用 IVW 法）。敏感性分析证实，这些发现对潜在的偏倚具有稳健性。
这些发现提供了遗传证据，表明较高的咖啡摄入量与 POAG 风险增加相关。鉴于咖啡的广泛消费，我们的发现为预防和管理 POAG 提供了新的见解。
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