Exploring causal correlations of inflammatory biomarkers in idiopathic normal-pressure hydrocephalus: insights from bidirectional Mendelian randomization analysis

doi:10.3389/fnagi.2024.1412434

科研成果详情

题名	Exploring causal correlations of inflammatory biomarkers in idiopathic normal-pressure hydrocephalus: insights from bidirectional Mendelian randomization analysis
作者	Jianglong Lu1; Xianpeng Wang1; Fanjie Xu1; Changjun Rao 2; Yuhang Guo 1; Zhipeng Su1; Siyan Chen3; Qun Li1
发表日期	2024
发表期刊	Frontiers in aging neuroscience 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Mendelian randomization biomarkers idiopathic normal-pressure hydrocephalus inflammation meta-analysis
其他关键词	CEREBROSPINAL-FLUID ; ALZHEIMERS-DISEASE ; RISK ; METALLOPROTEINASES ; NEURODEGENERATION ; EPIDEMIOLOGY ; EXPRESSION ; CYTOKINES
摘要	Neuroinflammatory processes have been identified as playing a crucial role in the pathophysiology of various neurodegenerative diseases, including idiopathic normal-pressure hydrocephalus (iNPH). iNPH, defined as a common disease of cognitive impairment in older adults, poses major challenges for therapeutic interventions owing to the stringent methodological requirements of relevant studies, clinical heterogeneity, unclear etiology, and uncertain diagnostic criteria. This study aims to assess the relationship between circulating inflammatory biomarkers and iNPH risk using bidirectional two-sample Mendelian randomization (MR) combined with meta-analysis., {AbstractText=In our bidirectional MR study, genetic data from a genome-wide association study (GWAS) involving 1,456 iNPH cases and 409,726 controls of European ancestry were employed. Single-nucleotide polymorphisms (SNPs) associated with exposures served as instrumental variables for estimating the causal relationships between iNPH and 132 types of circulating inflammatory biomarkers from corresponding GWAS data. Causal associations were primarily examined using the inverse variance-weighted method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode analyses. In the results, heterogeneity was assessed using the Cochran Q test. Horizontal pleiotropy was evaluated through the MR-Egger intercept test and the MR pleiotropy residual sum and outliers test. Sensitivity analysis was conducted through leave-one-out analysis. Reverse MR analyses were performed to mitigate bias from reverse causality. Meta-analyses of identical inflammatory biomarkers from both data sources strengthened the findings.}, {AbstractText=Results indicated a genetically predicted association between Interleukin-16 (IL-16) [OR: 1.228, 95% CI: 1.049-1.439, p = 0.011], TNF-related apoptosis ligand (TRAIL) [OR: 1.111, 95% CI: 1.019-1.210, p = 0.017] and Urokinase-type plasminogen activator (uPA) [OR: 1.303, 95% CI: 1.025-1.658, p = 0.031] and the risk of iNPH. Additionally, changes in human Glial cell line-derived neurotrophic factor (hGDNF) [OR: 1.044, 95% CI: 1.006-1.084, p = 0.023], Matrix metalloproteinase-1 (MMP-1) [OR: 1.058, 95% CI: 1.020, 1.098, p = 0.003] and Interleukin-12p70 (IL-12p70) [OR: 0.897, 95% CI: 0.946-0.997, p = 0.037] levels were identified as possible consequences of iNPH.}, Our MR study of inflammatory biomarkers and iNPH, indicated that IL-16, TRAIL, and uPA contribute to iNPH pathogenesis. Furthermore, iNPH may influence the expression of hGDNF, MMP-1, and IL-12p70. Therefore, targeting specific inflammatory biomarkers could be promising strategy for future iNPH treatment and prevention.
资助项目	Medical Health Science and Technology Research Project of Zhejiang Province of China [2023KY888]; Wenzhou Science and Technology Project [Y2020063]; Discipline Cluster of Oncology, Wenzhou Medical University, China [z2-2023016]
出版者	FRONTIERS MEDIA SA
ISSN	1663-4365
卷号	16
DOI	10.3389/fnagi.2024.1412434
页数	12
WOS类目	Geriatrics & Gerontology ; Neurosciences
WOS研究方向	Geriatrics & Gerontology ; Neurosciences & Neurology
WOS记录号	WOS:001262261300001
收录类别	PUBMED ; SCIE ; SCOPUS
URL	查看原文
PubMed ID	38974901
SCOPUSEID	2-s2.0-85197500926
通讯作者地址	[Li, Qun]Wenzhou Med Univ, Affiliated Hosp 1, Dept Neurosurg, Wenzhou, Peoples R China. ; [Chen, Siyan]Wenzhou Med Univ, Affiliated Hosp 1, Dept Neurol, Wenzhou, Peoples R China.
Scopus学科分类	Aging;Cognitive Neuroscience
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/215724
专题	附属第一医院_神经外科附属第一医院
作者单位	1.Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.; 2.Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.; 3.Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
第一作者单位	附属第一医院_神经外科
通讯作者单位	附属第一医院_神经外科; 第一临床医学院（信息与工程学院）、附属第一医院_内科学_神经内科
第一作者的第一单位	附属第一医院_神经外科
推荐引用方式 GB/T 7714	Jianglong Lu,Xianpeng Wang,Fanjie Xu,et al. Exploring causal correlations of inflammatory biomarkers in idiopathic normal-pressure hydrocephalus: insights from bidirectional Mendelian randomization analysis[J]. Frontiers in aging neuroscience,2024,16.
APA	Jianglong Lu., Xianpeng Wang., Fanjie Xu., Changjun Rao., Yuhang Guo., ... & Qun Li. (2024). Exploring causal correlations of inflammatory biomarkers in idiopathic normal-pressure hydrocephalus: insights from bidirectional Mendelian randomization analysis. Frontiers in aging neuroscience, 16.
MLA	Jianglong Lu,et al."Exploring causal correlations of inflammatory biomarkers in idiopathic normal-pressure hydrocephalus: insights from bidirectional Mendelian randomization analysis".Frontiers in aging neuroscience 16(2024).