ArticleBrain imaging and behavior2012
Genome-wide pathway analysis of memory impairment in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort implicates gene candidates, canonical pathways, and networks.
Article in Brain imaging and behavior, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 4 of them syntheses that pooled it.
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Who cites it
43 citing papers in PubMed, 4 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- A Meta-Analysis of Alzheimer's Disease Brain Transcriptomic Data.Journal of Alzheimer's disease : JAD · 2019Pooled it
- Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults.Journal of Alzheimer's disease : JAD · 2015Pooled it
- Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and biomarkers.Brain imaging and behavior · 2014Pooled it
- Pooled it
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- Role of adipocyte Na,K-ATPase oxidant amplification loop in cognitive decline and neurodegeneration.iScience · 2021Article
- Machine learning compensates fold-change method and highlights oxidative phosphorylation in the brain transcriptome of Alzheimer's disease.Scientific reports · 2021Article
- An epigenetic pathway in rice connects genetic variation to anaerobic germination and seedling establishment.Plant physiology · 2021Article
- Super-variants identification for brain connectivity.Human brain mapping · 2021Article
- Flavonoids Modulate the Accumulation of Toxins FromFrontiers in plant science · 2021Article
- Multivariate genome wide association and network analysis of subcortical imaging phenotypes in Alzheimer's disease.BMC genomics · 2020Article
- Association of microbiota-derived propionic acid and Alzheimer's disease; bioinformatics analysis.Journal of diabetes and metabolic disorders · 2020Article
- SP1-mediated upregulation of LINGO-1 promotes degeneration of retinal ganglion cells in optic nerve injury.CNS neuroscience & therapeutics · 2020Article
- Brain Imaging Genomics: Integrated Analysis and Machine Learning.Proceedings of the IEEE. Institute of Electrical and Electronics Engineers · 2020Article
- Genome-wide association analysis of hippocampal volume identifies enrichment of neurogenesis-related pathways.Scientific reports · 2019Article
- Biological Hallmarks of Cancer in Alzheimer's Disease.Molecular neurobiology · 2019Review
- GWAS and Beyond: Using Omics Approaches to Interpret SNP Associations.Current genetic medicine reports · 2019Article
- Targeted neurogenesis pathway-based gene analysis identifies ADORA2A associated with hippocampal volume in mild cognitive impairment and Alzheimer's disease.Neurobiology of aging · 2017Article
- Toward common mechanisms for risk factors in Alzheimer's syndrome.Alzheimer's & dementia (New York, N. Y.) · 2017Review
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Memory deficits are prominent features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). The genetic architecture underlying these memory deficits likely involves the combined effects of multiple genetic variants operative within numerous biological pathways. In order to identify functional pathways associated with memory impairment, we performed a pathway enrichment analysis on genome-wide association data from 742 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. A composite measure of memory was generated as the phenotype for this analysis by applying modern psychometric theory to item-level data from the ADNI neuropsychological test battery. Using the GSA-SNP software tool, we identified 27 canonical, expertly-curated pathways with enrichment (FDR-corrected p-value < 0.05) against this composite memory score. Processes classically understood to be involved in memory consolidation, such as neurotransmitter receptor-mediated calcium signaling and long-term potentiation, were highly represented among the enriched pathways. In addition, pathways related to cell adhesion, neuronal differentiation and guided outgrowth, and glucose- and inflammation-related signaling were also enriched. Among genes that were highly-represented in these enriched pathways, we found indications of coordinated relationships, including one large gene set that is subject to regulation by the SP1 transcription factor, and another set that displays co-localized expression in normal brain tissue along with known AD risk genes. These results 1) demonstrate that psychometrically-derived composite memory scores are an effective phenotype for genetic investigations of memory impairment and 2) highlight the promise of pathway analysis in elucidating key mechanistic targets for future studies and for therapeutic interventions.
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