循环脂肪酸与原发性开角型青光眼风险：一项孟德尔随机化研究。

Circulating fatty acids and risk of primary open-angle glaucoma: A mendelian randomization study.

机构信息

Department of Ophthalmology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, Zhejiang, China.

Department of Biochemistry and Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Hangzhou, Zhejiang, China.

出版信息

Gene. 2022 Feb 15;811:146078. doi: 10.1016/j.gene.2021.146078. Epub 2021 Nov 25.

DOI:10.1016/j.gene.2021.146078

PMID:34838945

Abstract

PURPOSE

The relationship between fatty acids (FAs) and glaucoma remains controversial despite several observational studies. We organized a mendelian randomization (MR) study to determine the genetic causal association between circulating FAs and primary open-angle glaucoma (POAG).

METHODS

The two-sample MR method was used to acquire causal estimates. Fourteen distinct single nucleotide polymorphisms (SNPs) of ten FAs were chosen as instrumental variables (IVs) at a genome-wide significance level (p < 5 × 10). Summary statistics for POAG were available from a genome-wide association meta-analysis of 216,257 individuals of European ancestry (16,677 cases, 199,580 controls). The inverse-variance weighted (IVW) method was adopted to evaluate the causality of FAs and POAG. Multiple sensitivity analyses were applied to avoid pleiotropy.

RESULTS

The IVW method suggested no evidence to support causal effects of ten FAs on POAG. The odds ratio (OR) per one SD increment of each FA was OR = 1.64 (95% CI, 0.441-6.098, p = 0.46), OR = 0.815 (95% CI, 0.604-1.101, p = 0.182), OR = 0.896 (95% CI, 0.669-1.198, p = 0.458), OR = 1.014 (95% CI, 0.801-1.283, p = 0.91), OR = 1.008 (95% CI, 0.971-1.045, p = 0.683), OR = 0.993 (95% CI, 0.973-1.013, p = 0.483), OR = 0.731 (95% CI, 0.261-2.048, p = 0.551), OR = 1.048 (95% CI, 0.934-1.175, p = 0.425), OR = 1.039 (95% CI, 0.903-1.196, p = 0.593), OR = 0.967 (95% CI, 0.879-1.062, p = 0.477). Moreover, Sensitivity analysis indicated no pleiotropy.

CONCLUSION

This MR study does not support causal associations between ten FAs and POAG.

摘要

目的

尽管有几项观察性研究，但脂肪酸（FA）与青光眼之间的关系仍存在争议。我们组织了一项孟德尔随机化（MR）研究，以确定循环 FA 与原发性开角型青光眼（POAG）之间的遗传因果关系。

方法

使用两样本 MR 方法获取因果估计值。选择十种 FA 的十四个不同的单核苷酸多态性（SNP）作为全基因组显著水平（p < 5 × 10）的工具变量（IV）。欧洲血统的 216,257 名个体的全基因组关联荟萃分析提供了 POAG 的汇总统计数据（16,677 例病例，199,580 例对照）。采用逆方差加权（IVW）法评估 FA 和 POAG 的因果关系。进行了多种敏感性分析以避免混杂。

结果

IVW 方法没有证据表明十种 FA 对 POAG 有因果影响。每种 FA 的一个标准差增量的优势比（OR）为 OR = 1.64（95%CI，0.441-6.098，p = 0.46），OR = 0.815（95%CI，0.604-1.101，p = 0.182），OR = 0.896（95%CI，0.669-1.198，p = 0.458），OR = 1.014（95%CI，0.801-1.283，p = 0.91），OR = 1.008（95%CI，0.971-1.045，p = 0.683），OR = 0.993（95%CI，0.973-1.013，p = 0.483），OR = 0.731（95%CI，0.261-2.048，p = 0.551），OR = 1.048（95%CI，0.934-1.175，p = 0.425），OR = 1.039（95%CI，0.903-1.196，p = 0.593），OR = 0.967（95%CI，0.879-1.062，p = 0.477）。此外，敏感性分析表明没有混杂。