SynthesisPloS one2014
Overrepresentation of glutamate signaling in Alzheimer's disease: network-based pathway enrichment using meta-analysis of genome-wide association studies.
Synthesis in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Genetic Variability in Molecular Pathways Implicated in Alzheimer's Disease: A Comprehensive Review.Frontiers in aging neuroscience · 2021Pooled it
- Linking Alzheimer's disease and type 2 diabetes: Novel shared susceptibility genes detected by cFDR approach.Journal of the neurological sciences · 2017Pooled it
- Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.Molecular neurobiology · 2016Pooled it
- New Genetic Associations Between Alzheimer's Disease and Its Key Risk Factors.Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society · 2026Article
- Glutamate stress in the caudal nucleus tractus solitarii (nTS): Impact on respiratory function and synaptic signaling in an Alzheimer's disease model.Experimental neurology · 2025Article
- An Expanded Narrative Review of Neurotransmitters on Alzheimer's Disease: The Role of Therapeutic Interventions on Neurotransmission.Molecular neurobiology · 2025Review
- From genomic discovery to application in age-related hearing loss: a global bibliometric and cross-ethnic analysis.Frontiers in aging neuroscience · 2025Article
- An EWAS of dementia biomarkers and their associations with age, African ancestry, and PTSD.Clinical epigenetics · 2024Article
- Recent Trends in Active and Passive Immunotherapies of Alzheimer's Disease.Antibodies (Basel, Switzerland) · 2023Review
- Endosomal Acid-Base Homeostasis in Neurodegenerative Diseases.Reviews of physiology, biochemistry and pharmacology · 2023Article
- The Big Picture of Neurodegeneration: A Meta Study to Extract the Essential Evidence on Neurodegenerative Diseases in a Network-Based Approach.Frontiers in aging neuroscience · 2022Article
- Lithium modulates multiple tau kinases with distinct effects in cortical and hippocampal neurons according to concentration ranges.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Glutamate and GABA in Microglia-Neuron Cross-Talk in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Gene Ontology curation of the blood-brain barrier to improve the analysis of Alzheimer's and other neurological diseases.Database : the journal of biological databases and curation · 2021Article
- Cognitive function: holarchy or holacracy?Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Review
- Risk Variants in Three Alzheimer's Disease Genes Show Association with EEG Endophenotypes.Journal of Alzheimer's disease : JAD · 2021Article
- Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale.Cells · 2020Article
- Association of Uncommon, Noncoding Variants in the APOE Region With Risk of Alzheimer Disease in Adults of European Ancestry.JAMA network open · 2020Article
- A telescope GWAS analysis strategy, based on SNPs-genes-pathways ensamble and on multivariate algorithms, to characterize late onset Alzheimer's disease.Scientific reports · 2020Article
- Neuronal-Glial Interaction in a Triple-Transgenic Mouse Model of Alzheimer's Disease: Gene Ontology and Lithium Pathways.Frontiers in neuroscience · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Genome-wide association studies (GWAS) have successfully identified several risk loci for Alzheimer's disease (AD). Nonetheless, these loci do not explain the entire susceptibility of the disease, suggesting that other genetic contributions remain to be identified. Here, we performed a meta-analysis combining data of 4,569 individuals (2,540 cases and 2,029 healthy controls) derived from three publicly available GWAS in AD and replicated a broad genomic region (>248,000 bp) associated with the disease near the APOE/TOMM40 locus in chromosome 19. To detect minor effect size contributions that could help to explain the remaining genetic risk, we conducted network-based pathway analyses either by extracting gene-wise p-values (GW), defined as the single strongest association signal within a gene, or calculated a more stringent gene-based association p-value using the extended Simes (GATES) procedure. Comparison of these strategies revealed that ontological sub-networks (SNs) involved in glutamate signaling were significantly overrepresented in AD (p<2.7×10(-11), p<1.9×10(-11); GW and GATES, respectively). Notably, glutamate signaling SNs were also found to be significantly overrepresented (p<5.1×10(-8)) in the Alzheimer's disease Neuroimaging Initiative (ADNI) study, which was used as a targeted replication sample. Interestingly, components of the glutamate signaling SNs are coordinately expressed in disease-related tissues, which are tightly related to known pathological hallmarks of AD. Our findings suggest that genetic variation within glutamate signaling contributes to the remaining genetic risk of AD and support the notion that functional biological networks should be targeted in future therapies aimed to prevent or treat this devastating neurological disorder.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.