ArticlePLoS genetics2021
Hippocampal transcriptome-wide association study and neurobiological pathway analysis for Alzheimer's disease.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- Golgi dysfunction in Alzheimer disease: from human multiomic signatures to therapeutic targets.Experimental & molecular medicine · 2026Review
- Transcriptome-wide association analysis of Alzheimer's disease: construction and clinical validation of transcriptomic risk scores.European archives of psychiatry and clinical neuroscience · 2026Article
- Circadian transcriptomic disruptions in the hippocampus precede cognitive deficits in a mouse model of Alzheimer's disease.Neural regeneration research · 2026Article
- Cell-type-aware transcriptome-wide association studies identify 91 independent risk genes for Alzheimer's disease dementia.Communications biology · 2026Article
- scTWAS: a powerful statistical framework for single-cell transcriptome-wide association studies.Nature communications · 2026Article
- RNA-seq variants reveal distinct patterns in the aging epitranscriptome: an in-depth analysis of age-matched Alzheimer's Disease patients and a cognitively normal cohort.bioRxiv : the preprint server for biology · 2026Article
- Decoding Alzheimer's Disease One Cell Class at a Time.Cellular and molecular neurobiology · 2026Review
- Integrative transcriptome-wide association analyses reveal PRKCG-linked GABAergic dysfunction in Fragile X-associated tremor/ataxia syndrome.Nature communications · 2026Article
- Epidemiological relevant effect biomarkers for thyroid hormone system related adverse outcome pathways: a literature review.Frontiers in pharmacology · 2026Review
- Integrative multi-omics approaches identify molecular pathways and improve Alzheimer's disease risk prediction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- scTWAS: A powerful statistical framework for single-cell transcriptome-wide association studies.Research square · 2025Article
- Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer's Disease? A Review of Recent Pertinent Observations from Molecular Biology.International journal of molecular sciences · 2025Review
- A Module-Level Polygenic Risk Score-Based NetWAS Framework for Identifying AD Genetic Modules Mediated by Amygdala: An ADNI Study.International journal of molecular sciences · 2025Article
- Translational disease modeling of peripheral blood identifies type 2 diabetes biomarkers predictive of Alzheimer's disease.NPJ systems biology and applications · 2025Article
- Employing Informatics Strategies in Alzheimer's Disease Research: A Review from Genetics, Multiomics, and Biomarkers to Clinical Outcomes.Annual review of biomedical data science · 2024Review
- A review and analysis of key biomarkers in Alzheimer's disease.Frontiers in neuroscience · 2024Review
- Identification of candidate DNA methylation biomarkers related to Alzheimer's disease risk by integrating genome and blood methylome data.Translational psychiatry · 2023Article
- A simulative deep learning model of SNP interactions on chromosome 19 for predicting Alzheimer's disease risk and rates of disease progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Transcriptome-wide association studies: recent advances in methods, applications and available databases.Communications biology · 2023Review
- Bibliometric analysis of global research on the role of apolipoprotein E in Alzheimer's disease.Heliyon · 2023Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies (GWASs) have identified multiple susceptibility loci for Alzheimer's disease (AD), which is characterized by early and progressive damage to the hippocampus. However, the association of hippocampal gene expression with AD and the underlying neurobiological pathways remain largely unknown. Based on the genomic and transcriptomic data of 111 hippocampal samples and the summary data of two large-scale meta-analyses of GWASs, a transcriptome-wide association study (TWAS) was performed to identify genes with significant associations between hippocampal expression and AD. We identified 54 significantly associated genes using an AD-GWAS meta-analysis of 455,258 individuals; 36 of the genes were confirmed in another AD-GWAS meta-analysis of 63,926 individuals. Fine-mapping models further prioritized 24 AD-related genes whose effects on AD were mediated by hippocampal expression, including APOE and two novel genes (PTPN9 and PCDHA4). These genes are functionally related to amyloid-beta formation, phosphorylation/dephosphorylation, neuronal apoptosis, neurogenesis and telomerase-related processes. By integrating the predicted hippocampal expression and neuroimaging data, we found that the hippocampal expression of QPCTL and ERCC2 showed significant difference between AD patients and cognitively normal elderly individuals as well as correlated with hippocampal volume. Mediation analysis further demonstrated that hippocampal volume mediated the effect of hippocampal gene expression (QPCTL and ERCC2) on AD. This study identifies two novel genes associated with AD by integrating hippocampal gene expression and genome-wide association data and reveals candidate hippocampus-mediated neurobiological pathways from gene expression to AD.
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