ArticleBMC medical genomics2019
Enhancer variants associated with Alzheimer's disease affect gene expression via chromatin looping.
Article in BMC medical genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Guidelines for bioinformatics of single-cell sequencing data analysis in Alzheimer's disease: review, recommendation, implementation and application.Molecular neurodegeneration · 2022Pooled it
- Causal relationships between alzheimer's disease genetics and brain connectivity alterations: a multi-modal mendelian randomization study with transcriptomic validation of 191 rs-fMRI and 635 DTI neuroimaging traits.Brain imaging and behavior · 2026Article
- Multiple human enhancer RNAs contain long translated open reading frames.Genes & development · 2025Article
- GWAS Identifies SNPs Associated With Severe Adverse Events and Efficacy in Advanced Renal Cell Carcinoma Treated With Nivolumab.Cancer science · 2025Article
- Exploration of biomarkers of Alzheimer's disease based on orthogonal multi-task canonical correlation analysis.BMC medical imaging · 2025Article
- Neur-Ally: a deep learning model for regulatory variant prediction based on genomic and epigenomic features in brain and its validation in certain neurological disorders.NAR genomics and bioinformatics · 2025Article
- DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer´s disease.Cellular and molecular life sciences : CMLS · 2025Article
- Non-coding variation in dementias: mechanisms, insights, and challenges.NPJ dementia · 2025Review
- Identification and Copy Number Variant Analysis of Enhancer Regions of Genes Causing Spinocerebellar Ataxia.International journal of molecular sciences · 2024Article
- Connecting dementia risk loci to the CSF proteome identifies pathophysiological leads for dementia.Brain : a journal of neurology · 2024Article
- Gene networks and systems biology in Alzheimer's disease: Insights from multi-omics approaches.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- An Emerging Role for Enhancer RNAs in Brain Disorders.Neuromolecular medicine · 2024Review
- Integrative single-nucleus multi-omics analysis prioritizes candidate cis and trans regulatory networks and their target genes in Alzheimer's disease brains.Cell & bioscience · 2023Article
- Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
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- Zebrafish regulatory genomic resources for disease modelling and regeneration.Disease models & mechanisms · 2023Article
- 3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus.Annals of the rheumatic diseases · 2023Article
- Three-dimensional chromatin architecture datasets for aging and Alzheimer's disease.Scientific data · 2023Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGenome-wide association studies (GWASs) have identified single-nucleotide polymorphisms (SNPs) that may be genetic factors underlying Alzheimer's disease (AD). However, how these AD-associated SNPs (AD SNPs) contribute to the pathogenesis of this disease is poorly understood because most of them are located in non-coding regions, such as introns and intergenic regions. Previous studies reported that some disease-associated SNPs affect regulatory elements including enhancers. We hypothesized that non-coding AD SNPs are located in enhancers and affect gene expression levels via chromatin loops.
methodsTo characterize AD SNPs within non-coding regions, we extracted 406 AD SNPs with GWAS p-values of less than 1.00 × 10
resultsWe report the following findings: (1) nearly 30% of non-coding AD SNPs are located in enhancers; (2) eQTL genes affected by non-coding AD SNPs within enhancers are associated with amyloid beta clearance, synaptic transmission, and immune responses; (3) 95% of the AD SNPs located in enhancers co-localize with their eQTL genes in topologically associating domains suggesting that regulation may occur through chromatin higher-order structures; (4) rs1476679 spatially contacts the promoters of eQTL genes via CTCF-CTCF interactions; (5) the effect of other AD SNPs such as rs7364180 is likely to be, at least in part, indirect through regulation of transcription factors that in turn regulate AD associated genes.
conclusionOur results suggest that non-coding AD SNPs may affect the function of enhancers thereby influencing the expression levels of surrounding or distant genes via chromatin loops. This result may explain how some non-coding AD SNPs contribute to AD pathogenesis.
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