ArticlePloS one2009
Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer's disease.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers, 6 of them syntheses that pooled it.
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Who cites it
227 citing papers in PubMed, 6 syntheses or guidelines pooled it, 383 citations in OpenAlex.
- The global research of magnetic resonance imaging in Alzheimer's disease: a bibliometric analysis from 2004 to 2023.Frontiers in neurology · 2024Pooled it
- Role of Imaging Genetics in Alzheimer's Disease: A Systematic Review and Current Update.CNS & neurological disorders drug targets · 2024Pooled it
- Dissecting Complex and Multifactorial Nature of Alzheimer's Disease Pathogenesis: a Clinical, Genomic, and Systems Biology Perspective.Molecular neurobiology · 2016Pooled it
- Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and biomarkers.Brain imaging and behavior · 2014Pooled it
- Investigation of 15 of the top candidate genes for late-onset Alzheimer's disease.Human genetics · 2011Pooled it
- Pooled it
- A Genome-Wide Association Study Suggests Novel Loci Associated with a Schizophrenia-Related Brain-Based Phenotype.PloS one · 2013Trial
- Genetic analysis of imaging-derived phenotypes.Nature reviews. Genetics · 2026Review
- Genetic variation in the glymphatic pathway predicts cognition and neurodegeneration in preclinical Alzheimer's disease.Research square · 2026Article
- Methylomic signatures of tau and amyloid-beta in transgenic mouse models of Alzheimer's disease neuropathology.NPJ dementia · 2026Article
- Dysfunctional Chondroitin 4-Cells · 2025Article
- SENP6 Maintains Mitochondrial Homeostasis by Regulating Mitochondrial Protein Import Through deSUMOylation of TOM40.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring the relationship between methylation of the cortisol receptor genes and brain and cognitive outcomes in individuals with elevated amyloid-β.Research square · 2025Article
- snCED-seq: high-fidelity cryogenic enzymatic dissociation of nuclei for single-nucleus RNA-seq of FFPE tissues.Nature communications · 2025Article
- TOMM40 may mediate GFAP, neurofilament light Protein, pTau181, and brain morphometry in aging.Aging brain · 2025Article
- Newly Identified Genetic Associations of Alzheimer Disease by Conditional Selective Inference: Potential Implications for the Tau Hypothesis.Bioinformatics and biology insights · 2025Article
- Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes.Journal of neuroinflammation · 2024Article
- A novel classification framework for genome-wide association study of whole brain MRI images using deep learning.PLoS computational biology · 2024Article
- The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders.Nature communications · 2024Article
- Differential methylation analysis in neuropathologically confirmed dementia with Lewy bodies.Communications biology · 2024Article
167 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundWith the exception of APOE epsilon4 allele, the common genetic risk factors for sporadic Alzheimer's Disease (AD) are unknown. METHODS AND
findingsWe completed a genome-wide association study on 381 participants in the ADNI (Alzheimer's Disease Neuroimaging Initiative) study. Samples were genotyped using the Illumina Human610-Quad BeadChip. 516,645 unique Single Nucleotide Polymorphisms (SNPs) were included in the analysis following quality control measures. The genotype data and raw genetic data are freely available for download (LONI, http://www.loni.ucla.edu/ADNI/Data/). Two analyses were completed: a standard case-control analysis, and a novel approach using hippocampal atrophy measured on MRI as an objectively defined, quantitative phenotype. A General Linear Model was applied to identify SNPs for which there was an interaction between the genotype and diagnosis on the quantitative trait. The case-control analysis identified APOE and a new risk gene, TOMM40 (translocase of outer mitochondrial membrane 40), at a genome-wide significance level of < or =10(-6) (10(-11) for a haplotype). TOMM40 risk alleles were approximately twice as frequent in AD subjects as controls. The quantitative trait analysis identified 21 genes or chromosomal areas with at least one SNP with a p-value < or =10(-6), which can be considered potential "new" candidate loci to explore in the etiology of sporadic AD. These candidates included EFNA5, CAND1, MAGI2, ARSB, and PRUNE2, genes involved in the regulation of protein degradation, apoptosis, neuronal loss and neurodevelopment. Thus, we identified common genetic variants associated with the increased risk of developing AD in the ADNI cohort, and present publicly available genome-wide data. Supportive evidence based on case-control studies and biological plausibility by gene annotation is provided. Currently no available sample with both imaging and genetic data is available for replication.
conclusionsUsing hippocampal atrophy as a quantitative phenotype in a genome-wide scan, we have identified candidate risk genes for sporadic Alzheimer's disease that merit further investigation.
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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.