Circulating Inflammatory Proteins and Age-related Macular Degeneration: New Insights from Mendelian Randomization.

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Yujin Guo, Jing Zhao, Zhiqing Chen
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引用次数: 0

Abstract

Background: Inflammation is a key mechanism underlying age-related macular degeneration (AMD); however, the specific circulating inflammatory proteins involved remain unclear. This study investigated the causal relationship between 91 circulating inflammatory proteins and AMD using a two-sample Mendelian randomization (MR) approach.

Methods: We conducted a two-sample magnetic resonance imaging MR analysis using genomewide association study (GWAS) data. Five MR methodologies were applied, with inverse variance weighting (IVW) as the primary approach. We applied false discovery rate (FDR) correction to mitigate false positives. Sensitivity analyses were performed to assess horizontal pleiotropy and heterogeneity. Additionally, Steiger's test, reverse MR analysis, and linkage disequilibrium score regression (LDSC) were used to validate the results.

Results: Five inflammatory proteins demonstrated significant associations with overall AMD, including three associated with wet AMD and one associated with dry AMD. LDSC analysis indicated that, except for fibroblast growth factor-19, no genetic correlation confounded the causal relationships. Additionally, the expression of the identified proteins was unaffected by the genetic prediction of AMD.

Conclusion: This study highlights the causal relationship between specific inflammatory proteins and AMD, emphasizing their potential roles in AMD pathogenesis and potential therapeutic targets.

循环炎症蛋白和年龄相关性黄斑变性:孟德尔随机化的新见解。
背景:炎症是老年性黄斑变性(AMD)的关键机制;然而,所涉及的特定循环炎症蛋白仍不清楚。本研究采用双样本孟德尔随机化(MR)方法调查了91种循环炎症蛋白与AMD之间的因果关系。方法:我们使用全基因组关联研究(GWAS)数据进行了两样本磁共振成像MR分析。采用五种MR方法,以逆方差加权(IVW)为主要方法。我们应用错误发现率(FDR)校正来减少误报。进行敏感性分析以评估水平多效性和异质性。此外,使用Steiger检验、反向MR分析和连锁不平衡评分回归(LDSC)来验证结果。结果:五种炎症蛋白与整体AMD有显著相关性,其中三种与湿性AMD相关,一种与干性AMD相关。LDSC分析表明,除成纤维细胞生长因子-19外,没有遗传相关性混淆因果关系。此外,鉴定的蛋白的表达不受AMD遗传预测的影响。结论:本研究强调了特异性炎症蛋白与AMD之间的因果关系,强调了它们在AMD发病机制中的潜在作用和潜在的治疗靶点。
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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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