代谢物与年龄相关性黄斑变性之间的因果关联：一项双向两样本孟德尔随机化研究

Causal association between metabolites and age-related macular degeneration: a bidirectional two-sample mendelian randomization study.

作者信息

Liu Zhen-Yu, Zhang Hang, Sun Xiu-Li, Liu Jian-Ying

机构信息

Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, No. 1, Dongjiaomin Lane, Dongcheng District, Beijing, 100730, China.

出版信息

Hereditas. 2024 Dec 20;161(1):51. doi: 10.1186/s41065-024-00356-6.

DOI:10.1186/s41065-024-00356-6

PMID:39707561

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11662531/

Abstract

BACKGROUND

Age-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly population. Accumulating evidence has revealed the possible association between metabolites and AMD. This study aimed to assess the effect of plasma metabolites on AMD and its two subtypes using a bidirectional two-sample Mendelian randomization approach.

METHODS

The causality between plasma metabolites and AMD was assessed by a bidirectional two-sample Mendelian randomization (MR) analysis using the genome-wide association studies (GWAS) summary statistics of 1400 genetically determined metabolites (GDMs) and AMD. For this MR analysis, inverse variance weighted (IVW) was used as the primary method, with weighted median, MR-Egger, weighted mode, and simple mode as supplementary methods to examine the causality. MR-Egger intercept, Cochran's Q, and MR-PRESSO test were employed to evaluate possible pleiotropy and heterogeneity.

RESULTS

The results of IVW showed significant causal associations between 13 GDMs and AMD. 1-stearoyl-GPE (18:0), androstenediol (3β,17β) monosulfate, stearoyl sphingomyelin (d18:1/18:0), xylose, and X-11,850 exhibited a protective effect on AMD, while gulonate and mannonate increased the risk of AMD. 1-stearoyl-GPE (18:0) and X-11,850 exhibited protective effects on dry AMD. DHEAS, 1-stearoyl-GPE (18:0), 5α-androstan-3β,17β-diol disulfate, xylose, androstenediol (3β,17β) monosulfate, and N2-acetyl, N6, N6-dimethyllysine exhibited a protective effect on wet AMD, while succinimide, 16a-hydroxy DHEA 3-sulfate, and X-13,553 increased the risk of wet AMD. Horizontal pleiotropy and heterogeneity did not distort the causal estimates. In the reverse MR analysis, AMD reduced the androstenediol (3β,17β) monosulfate level, and increased the stearoyl sphingomyelin(d18:1/18:0) level.

CONCLUSION

This study supported the effect of plasma metabolites on AMD, providing novel insights for clinical diagnosis and prevention strategy.

摘要

背景

年龄相关性黄斑变性（AMD）是老年人群视力损害的主要原因。越来越多的证据揭示了代谢物与AMD之间可能存在的关联。本研究旨在使用双向双样本孟德尔随机化方法评估血浆代谢物对AMD及其两种亚型的影响。

方法

利用1400种基因决定代谢物（GDM）和AMD的全基因组关联研究（GWAS）汇总统计数据，通过双向双样本孟德尔随机化（MR）分析评估血浆代谢物与AMD之间的因果关系。对于该MR分析，采用逆方差加权（IVW）作为主要方法，加权中位数、MR-Egger、加权模式和简单模式作为补充方法来检验因果关系。采用MR-Egger截距、Cochran's Q和MR-PRESSO检验评估可能的多效性和异质性。

结果

IVW结果显示13种GDM与AMD之间存在显著的因果关联。1-硬脂酰-GPE（18:0）、硫酸雄烯二醇（3β,17β）、硬脂酰鞘磷脂（d18:1/18:0）、木糖和X-11,850对AMD具有保护作用，而古洛糖酸和甘露糖酸增加了AMD的风险。1-硬脂酰-GPE（18:0）和X-11,850对干性AMD具有保护作用。硫酸脱氢表雄酮、1-硬脂酰-GPE（18:0）、5α-雄甾烷-3β,17β-二醇二硫酸盐、木糖、硫酸雄烯二醇（3β,17β）和N2-乙酰基、N6、N6-二甲基赖氨酸对湿性AMD具有保护作用，而琥珀酰亚胺、16α-羟基硫酸脱氢表雄酮3-硫酸盐和X-13,553增加了湿性AMD的风险。水平多效性和异质性并未扭曲因果估计。在反向MR分析中，AMD降低了硫酸雄烯二醇（3β,17β）水平，并增加了硬脂酰鞘磷脂（d18:1/18:0）水平。