Differential Gene Analysis To Identify Risk Genes for Amyotrophic Lateral Sclerosis
DOI:
https://doi.org/10.58445/vbcy2411Keywords:
ALS, Neurodegenerative Disease, Gene AnalysisAbstract
ALS is a neurodegenerative disease that is projected to affect more than 375,000 people by the year 2040. Currently, the genetic drivers of sporadic ALS are poorly understood, which is why new approaches such as those that integrate data from multiple tissues may highlight specific signals that are not derived from a single tissue sample. This study uses differential analysis that has been applied to publicly available datasets to identify key genes that may be associated with ALS. By using sequencing data derived from both spinal cord tissue and the blood, this study aims to maximize the statistical confidence in the genes that are identified as contributing to ALS to allow for future research into the pathology of ALS. The findings of this study aim to expand on and/or corroborate the current understanding of the genetic role of genes in ALS to allow for further research into the complex neurodegenerative disease and the genes that lead to it. The finding of this study was that ALS is associated with an upregulation of the inflammatory response that results from certain genes. These inflammatory responses lead to damage and degeneration of motor neurons, with the permanent damage to these motor neurons inhibiting normal bodily activity, contributing to the symptoms of muscle weakness, paralysis, and even death. Twenty four of the top 100 genes were found to be part of the same neuron uptake process while also being significantly dysregulated in both the spinal cord and the blood. These genes were part of an inflammatory response pathway and with interferon gamma regulation in the neurons. These genes may serve as future biomarkers and therapeutic targets with this research's validation.
References
Amyotrophic Lateral Sclerosis (ALS) | National Institute of Neurological Disorders and Stroke, www.ninds.nih.gov/health-information/disorders/amyotrophic-lateral-sclerosis-als. Accessed 4 Oct. 2026.
“About Amyotrophic Lateral Sclerosis (ALS).” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.cdc.gov/als/abouttheregistrymain/about-amyotrophic-lateral-sclerosis-als.html. Accessed 4 Oct. 2026.
“History of Amyotrophic Lateral Sclerosis.” Fondation Ipsen, 3 Apr. 2025, www.fondation-ipsen.org/podcast/history-of-amyotrophic-lateral-sclerosis/.
Londral, Ana. “Assistive Technologies for communication empower patients with ALS to generate and self-report health data.” Frontiers in Neurology, vol. 13, 26 Apr. 2022, https://doi.org/10.3389/fneur.2022.867567.
“Causes/Inheritance - Amyotrophic Lateral Sclerosis (ALS) - Diseases.” Muscular Dystrophy Association, 24 Oct. 2025, www.mda.org/disease/amyotrophic-lateral-sclerosis/causes-inheritance.
Amyotrophic Lateral Sclerosis (ALS) | National Institute of Neurological Disorders and Stroke, www.ninds.nih.gov/health-information/disorders/amyotrophic-lateral-sclerosis-als. Accessed 4 Oct. 2026.
Ryan, Marie, et al. “Lifetime risk and heritability of amyotrophic lateral sclerosis.” JAMA Neurology, vol. 76, no. 11, 1 Nov. 2019, p. 1367, https://doi.org/10.1001/jamaneurol.2019.2044.
Vasta, Rosario, et al. “Amyotrophic lateral sclerosis prevalence projection in 2040: A less rare disease.” Annals of Clinical and Translational Neurology, vol. 13, no. 2, 14 Oct. 2025, pp. 379–386, https://doi.org/10.1002/acn3.70226.
Saitoh, Yuji, and Yuji Takahashi. “Riluzole for the treatment of amyotrophic lateral sclerosis.” Neurodegenerative Disease Management, vol. 10, no. 6, 27 Aug. 2020, pp. 343–355, https://doi.org/10.2217/nmt-2020-0033.
Center for Drug Evaluation and Research. “FDA Approves Treatment of ALS Associated with a Mutation in the Supero.” U.S. Food and Drug Administration, FDA, www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-amyotrophic-lateral-sclerosis-associated-mutation-sod1-gene. Accessed 4 Oct. 2026.
Williams, Kelly. “RNA Sequencing of Peripheral Blood in Amyotrophic Lateral Sclerosis Reveals Distinct Molecular Subtypes: Considerations for Biomarker Discovery.” NationalCenter for Biotechnology Information, U.S. National Library of Medicine, ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76220. Accessed 4 Oct. 2026.
Williams, Kelly. “RNA Sequencing of Peripheral Blood in Amyotrophic Lateral Sclerosis Reveals Distinct Molecular Subtypes: Considerations for Biomarker Discovery.” National Center for Biotechnology Information, U.S. National Library of Medicine, www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE234297. Accessed 4 Oct. 2026.
Cho, HaEun, and Surabhi Shukla. “Role of edaravone as a treatment option for patients with amyotrophic lateral sclerosis.” Pharmaceuticals, vol. 14, no. 1, 31 Dec. 2020, p. 29, https://doi.org/10.3390/ph14010029.
“Database Commons a Catalog of Worldwide Biological Databases.” STRING - Database Commons, ngdc.cncb.ac.cn/databasecommons/database/id/62. Accessed 4 Oct. 2026.
Gene Ontology Amigo, amigo.geneontology.org/amigo/landing. Accessed 4 Oct. 2026.
Kegg Pathway Database, www.genome.jp/kegg/pathway.html. Accessed 4 Oct. 2026.
Hartzfeld, Deborah. “FYI: Familial Amyotrophic Lateral Sclerosis (Fals) and Genetic Testing.” The ALS Association, 10 June 2020, www.als.org/navigating-als/resources/familial-amyotrophic-lateral-sclerosis-fals-and-genetic.
Zucca, Susanna, et al. “RNA-seq profiling in peripheral blood mononuclear cells of amyotrophic lateral sclerosis patients and controls.” Scientific Data, vol. 6, no. 1, 5 Feb. 2019, https://doi.org/10.1038/sdata.2019.6.
Masrori, Pegah, et al. “C9orf72 hexanucleotide repeat expansions impair microglial response in ALS.” Nature Neuroscience, vol. 28, no. 11, 14 Oct. 2025, pp. 2217–2230, https://doi.org/10.1038/s41593-025-02075-1.
Yao, H., et al. “OLR1 Knockdown Mitigates Traumatic-Hemorrhagic Shock-Induced Liver Injury by Inhibiting the TLR4/Myd88 Pathway and NLRP3 Inflammasome Activation - Molecular Biology.” SpringerLink, Pleiades Publishing, 21 July 2025, link.springer.com/article/10.1134/S0026893325600539.
OLR1 Gene Oxidized Low Density Lipoprotein Receptor 1, www.genecards.org/card/OLR1. Accessed 14 Oct. 2026.
Downloads
Posted
Categories
License
Copyright (c) 2026 Research Archive of Rising Scholars
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
