SynthesisNeuroscience2019
Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.
Synthesis in Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Dysregulated lactate metabolism synergizes with ALS genetic risk factors to accelerate motor decline.PloS one · 2026Article
- Dysregulated lactate metabolism synergizes with ALS genetic risk factors to accelerate motor decline.bioRxiv : the preprint server for biology · 2025Article
- Circular RNA expression in ALS is progressively deregulated and tissue-dependent.BMC genomics · 2025Article
- Sex-Specific Early Retinal Dysfunction in Mutant TDP-43 Transgenic Mice.Journal of Alzheimer's disease : JAD · 2024Article
- Dysautonomia in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2023Review
- The Serotonergic System and Amyotrophic Lateral Sclerosis: A Review of Current Evidence.Cellular and molecular neurobiology · 2023Review
- A chemogenomic approach is required for effective treatment of amyotrophic lateral sclerosis.Clinical and translational medicine · 2022Review
- BMP/TGF-β signaling as a modulator of neurodegeneration in ALS.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Retinal Damage in Amyotrophic Lateral Sclerosis: Underlying Mechanisms.Eye and brain · 2021Review
- Genetic modifiers and phenotypic variability in neuromuscular disorders.Journal of applied genetics · 2020Review
- Article
- Genetic modifiers ameliorate endocytic and neuromuscular defects in a model of spinal muscular atrophy.BMC biology · 2020Article
- From basic research to the clinic: innovative therapies for ALS and FTD in the pipeline.Molecular neurodegeneration · 2020Review
- New Roles for Canonical Transcription Factors in Repeat Expansion Diseases.Trends in genetics : TIG · 2020Review
- Phenotypic Suppression of ALS/FTD-Associated Neurodegeneration Highlights Mechanisms of Dysfunction.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Review
- Physiological, Pathological, and Targetable Membraneless Organelles in Neurons.Trends in neurosciences · 2019Review
- Motor Neuron Susceptibility in ALS/FTD.Frontiers in neuroscience · 2019Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that has significant overlap with frontotemporal dementia (FTD). Mutations in specific genes have been identified that can cause and/or predispose patients to ALS. However, the clinical variability seen in ALS patients suggests that additional genes impact pathology, susceptibility, severity, and/or progression of the disease. To identify molecular pathways involved in ALS, we undertook a meta-analysis of published genetic modifiers both in patients and in model organisms, and undertook bioinformatic pathway analysis. From 72 published studies, we generated a list of 946 genes whose perturbation (1) impacted ALS in patient populations, (2) altered defects in laboratory models, or (3) modified defects caused by ALS gene ortholog loss of function. Herein, these are all called modifier genes. We found 727 modifier genes that encode proteins with human orthologs. Of these, 43 modifier genes were identified as modifiers of more than one ALS gene/model, consistent with the hypothesis that shared genes and pathways may underlie ALS. Further, we used a gene ontology-based bioinformatic analysis to identify pathways and associated genes that may be important in ALS. To our knowledge this is the first comprehensive survey of ALS modifier genes. This work suggests that shared molecular mechanisms may underlie pathology caused by different ALS disease genes. Surprisingly, few ALS modifier genes have been tested in more than one disease model. Understanding genes that modify ALS-associated defects will help to elucidate the molecular pathways that underlie ALS and provide additional targets for therapeutic intervention.
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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.