ArticleAmerican journal of human genetics2017
A Dementia-Associated Risk Variant near TMEM106B Alters Chromatin Architecture and Gene Expression.
Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Genome-wide association study of cognitive function in diverse Hispanics/Latinos: results from the Hispanic Community Health Study/Study of Latinos.Translational psychiatry · 2020Pooled it
- Protective TMEM106B-rs3173615 delays age at onset in GRN mutation carriers.Molecular psychiatry · 2026Article
- Single-allele nanoscale mapping of regulatory variants.Nature genetics · 2026Article
- Clinical Associations of Cerebrospinal Fluid TMEM106B in Familial and Sporadic Frontotemporal Dementia.JAMA neurology · 2026Article
- Neurodegeneration risk variants promote lysosomal TMEM106B fibril accumulation.bioRxiv : the preprint server for biology · 2026Article
- Granulin loss and TMEM106B risk converge on lysosomal C-terminal fragment pathology in frontotemporal dementia.bioRxiv : the preprint server for biology · 2026Article
- The amyloidogenic C-terminal region of TMEM106B modulates lipid membrane biophysical properties: Functional and pathological insights.The Journal of biological chemistry · 2026Article
- Oxidative Stress and Lysosomal Dysfunction in Neurodegenerative Diseases: Underlying Mechanisms and Nanotherapeutic Targeting Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Divergent and convergent TMEM106B pathology in murine models of neurodegeneration and human disease.Acta neuropathologica communications · 2025Article
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- 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
- Increased TMEM106B levels lead to lysosomal dysfunction which affects synaptic signaling and neuronal health.Molecular neurodegeneration · 2025Article
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
- A common Alu insertion in the 3'UTR of TMEM106B is associated with risk of dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Cleaved TMEM106B forms amyloid aggregates in central and peripheral nervous systems.Acta neuropathologica communications · 2024Article
- CSPG4P12 polymorphism served as a susceptibility marker for esophageal cancer in Chinese population.BMC cancer · 2024Article
- TMEM106B C-terminal fragments aggregate and drive neurodegenerative proteinopathy.bioRxiv : the preprint server for biology · 2024Article
- Physiological and pathological functions of TMEM106B in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- TMEM106B coding variant is protective and deletion detrimental in a mouse model of tauopathy.Acta neuropathologica · 2024Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Neurodegenerative diseases pose an extraordinary threat to the world's aging population, yet no disease-modifying therapies are available. Although genome-wide association studies (GWASs) have identified hundreds of risk loci for neurodegeneration, the mechanisms by which these loci influence disease risk are largely unknown. Here, we investigated the association between common genetic variants at the 7p21 locus and risk of the neurodegenerative disease frontotemporal lobar degeneration. We showed that variants associated with disease risk correlate with increased expression of the 7p21 gene TMEM106B and no other genes; co-localization analyses implicated a common causal variant underlying both association with disease and association with TMEM106B expression in lymphoblastoid cell lines and human brain. Furthermore, increases in the amount of TMEM106B resulted in increases in abnormal lysosomal phenotypes and cell toxicity in both immortalized cell lines and neurons. We then combined fine-mapping, bioinformatics, and bench-based approaches to functionally characterize all candidate causal variants at this locus. This approach identified a noncoding variant, rs1990620, that differentially recruits CTCF in lymphoblastoid cell lines and human brain to influence CTCF-mediated long-range chromatin-looping interactions between multiple cis-regulatory elements, including the TMEM106B promoter. Our findings thus provide an in-depth analysis of the 7p21 locus linked by GWASs to frontotemporal lobar degeneration, nominating a causal variant and causal mechanism for allele-specific expression and disease association at this locus. Finally, we show that genetic variants associated with risk of neurodegenerative diseases beyond frontotemporal lobar degeneration are enriched in CTCF-binding sites found in brain-relevant tissues, implicating CTCF-mediated gene regulation in risk of neurodegeneration more generally.
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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.