ArticleNature2016
Parkinson-associated risk variant in distal enhancer of α-synuclein modulates target gene expression.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 329 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
329 citing papers in PubMed, 2 syntheses or guidelines pooled it, 522 citations in OpenAlex.
- Genome-wide Association and Meta-analysis of Age at Onset in Parkinson Disease: Evidence From the COURAGE-PD Consortium.Neurology · 2022Pooled it
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Brain region-resolved pharmacodynamics of an antisense oligonucleotide targeting human SNCA 3'UTR in BAC-hSNCA rats.Translational neurodegeneration · 2026Article
- CIDER: detecting changes in gene regulatory networks that are associated with changes in phenotype.bioRxiv : the preprint server for biology · 2026Article
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Neuronal titration of Snca via enhancer disruption mitigates disease onset in a Parkinson's disease mouse model.Brain : a journal of neurology · 2026Article
- iSCORE-PD: an isogenic stem cell collection to research Parkinson's disease.Nature communications · 2026Article
- Article
- Incense Aerosol-Induced Neurotoxicity Disrupts α-Synuclein Homeostasis in a Cellular Parkinson's Disease Model, Distinct from Cigarette Aerosols.Chemical research in toxicology · 2026Article
- ModelingbioRxiv : the preprint server for biology · 2026Article
- Enhancer-mediated Etv4 activation stimulates osteogenic differentiation.Nature communications · 2026Article
- Identifying drug targets for schizophrenia through gene prioritization.Translational psychiatry · 2026Article
- Epigenetic regulation in early embryogenesis: mechanisms, developmental programming, and transgenerational implications.Frontiers in cell and developmental biology · 2026Review
- De novo rare EMX2 variants lead to idiopathic hypogonadotropic hypogonadism.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- GWAS Identifies SNPs Associated With Severe Adverse Events and Efficacy in Advanced Renal Cell Carcinoma Treated With Nivolumab.Cancer science · 2025Article
- Alpha-Synuclein Neurobiology in Parkinson's Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives.Brain sciences · 2025Review
- Unveiling the regulatory potential of the non-coding genome: Insights from the human genome project to precision medicine.Genes & diseases · 2025Review
- Gene regulatory activity associated with polycystic ovary syndrome revealed DENND1A-dependent testosterone production.Nature communications · 2025Article
- Low-frequency genetic variants in GAK enhance Golgi function and protect against Parkinson's disease.medRxiv : the preprint server for health sciences · 2025Article
269 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Genome-wide association studies (GWAS) have identified numerous genetic variants associated with complex diseases, but mechanistic insights are impeded by a lack of understanding of how specific risk variants functionally contribute to the underlying pathogenesis. It has been proposed that cis-acting effects of non-coding risk variants on gene expression are a major factor for phenotypic variation of complex traits and disease susceptibility. Recent genome-scale epigenetic studies have highlighted the enrichment of GWAS-identified variants in regulatory DNA elements of disease-relevant cell types. Furthermore, single nucleotide polymorphism (SNP)-specific changes in transcription factor binding are correlated with heritable alterations in chromatin state and considered a major mediator of sequence-dependent regulation of gene expression. Here we describe a novel strategy to functionally dissect the cis-acting effect of genetic risk variants in regulatory elements on gene expression by combining genome-wide epigenetic information with clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9 genome editing in human pluripotent stem cells. By generating a genetically precisely controlled experimental system, we identify a common Parkinson's disease associated risk variant in a non-coding distal enhancer element that regulates the expression of α-synuclein (SNCA), a key gene implicated in the pathogenesis of Parkinson's disease. Our data suggest that the transcriptional deregulation of SNCA is associated with sequence-dependent binding of the brain-specific transcription factors EMX2 and NKX6-1. This work establishes an experimental paradigm to functionally connect genetic variation with disease-relevant phenotypes.
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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.