ArticleMolecular neurodegeneration2023
Genome-wide analyses identify NEAT1 as genetic modifier of age at onset of amyotrophic lateral sclerosis.
Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- The Prospective Regulatory Functions of lncRNAs and Their ceRNA Networks in the Development of Motor Neurons and Associated Diseases.Biomolecules · 2026Review
- Paraspeckle condensation is controlled via TDP-43 polymerization and linked to neuroprotection.Nature cell biology · 2026Article
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- Peripheral immune cells and glycation indices as potential diagnostic biomarkers in amyotrophic lateral sclerosis.Experimental biology and medicine (Maywood, N.J.) · 2026Article
- Unveiling the Genetic Association Between Hemoglobin Concentration and Amyotrophic Lateral Sclerosis.Brain and behavior · 2026Article
- Chromatin Meets Condensates: Emerging Interplays Linking Nuclear Paraspeckles to Gene Activation.Epigenetics reports · 2026Article
- A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS.Communications biology · 2025Article
- LncRNA levels in the central nervous system as novel potential players and biomarkers in amyotrophic lateral sclerosis.Non-coding RNA research · 2025Article
- Antisense oligonucleotide depletion ofmedRxiv : the preprint server for health sciences · 2025Article
- Decoding Neuromuscular Disorders: The Complex Role of Genetic and Epigenetic Regulators.Genes · 2025Review
- Investigating the role of inflammatory cytokines in mediating the effect of gut microbiota on gastrointestinal cancers: a mendelian randomization study.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Distinct expression of NEAT1 isoforms in Parkinson's disease models suggests different roles of the variants during the disease course.Scientific reports · 2025Article
- Identification of Novel Genetic Loci Affecting Age at Onset of Parkinson's Disease: A Genome-wide Association Study.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Retrotransposition-competent L1s are increased in the genomes of individuals with amyotrophic lateral sclerosis.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- A scoping review of statistical methods to investigate colocalization between genetic associations and microRNA expression in osteoarthritis.Osteoarthritis and cartilage open · 2024Article
- Differentially expressed lncRNAs in SOD1Open biology · 2024Article
- Article
- Peripheral immunity involvement in the cognitive impairment of sporadic amyotrophic lateral sclerosis.Frontiers in neurology · 2024Article
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients with amyotrophic lateral sclerosis (ALS) demonstrate great heterogeneity in the age at onset (AAO), which is closely related to the course of disease. However, most genetic studies focused on the risk of ALS, while the genetic background underlying AAO of ALS is still unknown.
methodsTo identify genetic determinants influencing AAO of ALS, we performed genome-wide association analysis using a Cox proportional hazards model in 2,841 patients with ALS (N
resultsThe total heritability of AAO of ALS was ~ 0.24. One novel locus rs10128627 (FRMD8) was significantly associated with earlier AAO by ~ 3.15 years (P = 1.54E-08, beta = 0.31, SE = 0.05). This locus was cis-eQTL of NEAT1 in multiple brain tissues and blood. Colocalization analysis detected association signals at this locus between AAO of ALS and expression of NEAT1. Furthermore, functional exploration supported the variant rs10128627 was associated with upregulated expression of NEAT1 in cell models and patients with ALS. Causal inference suggested higher total cholesterol, low-density lipoprotein, and eosinophil were nominally associated with earlier AAO of ALS, while monocyte might delay the AAO.
conclusionsCollective evidence from genetic, bioinformatic, and functional results suggested NEAT1 as a key player in the disease progression of ALS. These findings improve the current understanding of the genetic role in AAO of ALS, and provide a novel target for further research on the pathogenesis and therapeutic options to delay the disease onset.
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