Genome-wide genetic links between amyotrophic lateral sclerosis and autoimmune diseases
Open accessAbstract
Background: Epidemiological and clinical studies have suggested comorbidity between amyotrophic lateral sclerosis (ALS) and autoimmune disorders. However, little is known about their shared genetic architecture. Methods: To examine the relation between ALS and 10 autoimmune diseases, including asthma, celiac disease (CeD), Crohn’s disease (CD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and ulcerative colitis (UC), and identify shared risk loci, we first estimated the genetic correlation using summary statistics from genome-wide association studies, and then analyzed the genetic enrichment leveraging the conditional false discovery rate statistical method. Results: We identified a significant positive genetic correlation between ALS and CeD, MS, RA, and SLE, as well as a significant negative genetic correlation between ALS and IBD, UC, and CD. Robust genetic enrichment was observed between ALS and CeD and MS, and moderate enrichment was found between ALS and UC and T1D. Thirteen shared genetic loci were identified, among which five were suggestively significant in another ALS GWAS, namely rs3828599 (GPX3), rs3849943 (C9orf72), rs7154847 (G2E3), rs6571361 (SCFD1), and rs9903355 (GGNBP2). By integrating cis-expression quantitative trait loci analyses in Braineac and GTEx, we further identified GGNBP2,ATXN3, and SLC9A8 as novel ALS risk genes. Functional enrichment analysis indicated that the shared risk genes were involved in four pathways including membrane trafficking, vesicle-mediated transport, ER to Golgi anterograde transport, and transport to the Golgi and subsequent modification. Conclusions: Our findings demonstrate a specific genetic correlation between ALS and autoimmune diseases and identify shared risk loci, including three novel ALS risk genes. These results provide a better understanding for the pleiotropy of ALS and have implications for future therapeutic trials.
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A genome-wide association study demonstrated a specific genetic correlation between ALS and autoimmune diseases.
“A genome-wide association study also demonstrated a specific genetic correlation between ALS and autoimmune diseases.87”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [87]
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Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,380 · see citing works
The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
The GTEx Consortium, Ardlie, K. G., Deluca, D. S., Segrè, A. V., Sullivan, T. J., Young, T. R., Gelfand, E. T., Trowbridge, C. A., Maller, J. B., Tukiainen, T., et al. (2015) · Science · doi:10.1126/science.1262110 · Cited by 5,062 · see citing works
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336 · see citing works
Genomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162 · see citing works
Liu, J. Z., van Sommeren, S., Huang, H., Ng, S. C., Alberts, R., Takahashi, A., Ripke, S., Lee, J. C., Jostins, L., Shah, T., et al. (2015) · Nature Genetics · doi:10.1038/ng.3359 · Cited by 2,603 · see citing works
Brown, R. H., & Al‐Chalabi, A. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1603471 · Cited by 2,473 · see citing works
Nalls, M. A., Blauwendraat, C., Vallerga, C. L., Heilbron, K., Bandres-Ciga, S., Chang, D., Tan, M., Kia, D. A., Noyce, A. J., Xue, A., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30320-5 · Cited by 2,454 · see citing works
Genetics of rheumatoid arthritis contributes to biology and drug discovery
the RACI consortium, Okada, Y., the GARNET consortium, Wu, D., Trynka, G., Raj, T., Terao, C., Ikari, K., Kochi, Y., Ohmura, K., et al. (2014) · Nature · doi:10.1038/nature12873 · Cited by 2,310 · see citing works
How neuroinflammation contributes to neurodegeneration
Ransohoff, R. M. (2016) · Science · doi:10.1126/science.aag2590 · Cited by 1,967 · see citing works
Gut microbiota and IBD: causation or correlation?
Ni, J., Wu, G. D., Albenberg, L., & Tomov, V. T. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.88 · Cited by 1,778 · see citing works
The Type 1 Diabetes Genetics Consortium, Barrett, J. C., Clayton, D. G., Concannon, P., Akolkar, B., Cooper, J. D., Erlich, H. A., Julier, C., Morahan, G., Nerup, J., et al. (2009) · Nature Genetics · doi:10.1038/ng.381 · Cited by 1,746 · see citing works
Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility
International Multiple Sclerosis Genetics Consortium, Patsopoulos, N. A., Baranzini, S. E., Santaniello, A., Shoostari, P., Cotsapas, C., Wong, G., Beecham, A. H., James, T., Replogle, J., et al. (2019) · Science · doi:10.1126/science.aav7188 · Cited by 1,471 · see citing works
de Lange, K. M., Moutsianas, L., Lee, J. C., Lamb, C. A., Luo, Y., Kennedy, N. A., Jostins, L., Rice, D. L., Gutierrez-Achury, J., Ji, S.-G., et al. (2017) · Nature Genetics · doi:10.1038/ng.3760 · Cited by 1,445 · see citing works
van Es, M. A., Hardiman, O. M., Chiò, A., Al‐Chalabi, A., Pasterkamp, R. J., Veldink, J. H., & van den Berg, L. H. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31287-4 · Cited by 1,305 · see citing works
Molecular biology of amyotrophic lateral sclerosis: insights from genetics
Pasinelli, P., & Brown, R. H. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1971 · Cited by 1,107 · see citing works
Multiple common variants for celiac disease influencing immune gene expression
Dubois, P. C. A., Trynka, G., Franke, L., Hunt, K. A., Romanos, J., Curtotti, A., Zhernakova, A., Heap, G., Ádány, R., Aromaa, A. J., et al. (2010) · Nature Genetics · doi:10.1038/ng.543 · Cited by 1,026 · see citing works
Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity
Collaborative Association Study of Psoriasis (CASP), Tsoi, L. C., Genetic Analysis of Psoriasis Consortium, Psoriasis Association Genetics Extension, Wellcome Trust Case Control Consortium 2, Spain, S. L., Knight, J., Ellinghaus, E., Stuart, P. E., Capon, F., et al. (2012) · Nature Genetics · doi:10.1038/ng.2467 · Cited by 1,024 · see citing works
Bentham, J., Morris, D. L., Graham, D. S. C., Pinder, C. L., Tombleson, P., Behrens, T. W., Martin, J. J., Fairfax, B. P., Knight, J. C., Chen, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3434 · Cited by 990 · see citing works
Inflammation in CNS neurodegenerative diseases
Stephenson, J., Nutma, E., van der Valk, P., & Amor, S. (2018) · Immunology · doi:10.1111/imm.12922 · Cited by 966 · see citing works
Trynka, G., PreventCD Study Group, Hunt, K. A., Bockett, N. A., Romanos, J., Mistry, V., Szperl, A., Bakker, S. F., Bardella, M. T., Bhaw, L., et al. (2011) · Nature Genetics · doi:10.1038/ng.998 · Cited by 825 · see citing works
ConsensusPathDB: toward a more complete picture of cell biology
Kamburov, A., Pentchev, K., Galicka, H., Wierling, C., Lehrach, H., & Herwig, R. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq1156 · Cited by 671 · see citing works
Genome-Wide Analyses Identify KIF5A as a Novel ALS Gene
Nicolas, A., Kenna, K. P., Renton, A. E., Ticozzi, N., Faghri, F., Chia, R., Dominov, J. A., Kenna, B., Nalls, M. A., Keagle, P. J., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.027 · Cited by 670 · see citing works
NOD proteins: regulators of inflammation in health and disease
Philpott, D. J., Sorbara, M. T., Robertson, S. J., Croitoru, K., & Girardin, S. E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3565 · Cited by 668 · see citing works
Genetic variability in the regulation of gene expression in ten regions of the human brain
UK Brain Expression Consortium, Ramasamy, A., North American Brain Expression Consortium, Trabzuni, D., Guelfi, S., Varghese, V., Smith, C., Walker, R., De, T., Coin, L., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3801 · Cited by 644 · see citing works
Genomic inflation factors under polygenic inheritance
Yang, J., Weedon, M. N., Purcell, S., Lettre, G., Estrada, K., Willer, C. J., Smith, A. V., Ingelsson, E., O’Connell, J. R., Mangino, M., et al. (2011) · European Journal of Human Genetics · doi:10.1038/ejhg.2011.39 · Cited by 560 · see citing works
Yiangou, Y., Facer, P., Durrenberger, P., Chessell, I. P., Naylor, A., Bountra, C., Banati, R. R., & Anand, P. (2006) · BMC Neurology · doi:10.1186/1471-2377-6-12 · Cited by 509 · see citing works
Andreassen, O. A., Djurovic, S., Thompson, W. K., Schork, A. J., Kendler, K. S., O’Donovan, M. C., Rujescu, D., Werge, T., van de Bunt, M., Morris, A. P., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.01.001 · Cited by 506 · see citing works
Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs
Jaiswal, M. K. (2018) · Medicinal Research Reviews · doi:10.1002/med.21528 · Cited by 456 · see citing works
Size, power and false discovery rates
Efron, B. (2007) · The Annals of Statistics · doi:10.1214/009053606000001460 · Cited by 436 · see citing works
Andreassen, O. A., Thompson, W. K., Schork, A. J., Ripke, S., Mattingsdal, M., Kelsoe, J. R., Kendler, K. S., O’Donovan, M. C., Rujescu, D., Werge, T. M., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003455 · Cited by 402 · see citing works
Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies
Beers, D. R., & Appel, S. H. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30394-6 · Cited by 387 · see citing works
Inhibition of Microglial Phagocytosis Is Sufficient To Prevent Inflammatory Neuronal Death
Neher, J. J., Neniskyte, U., Zhao, J.-W., Bal-Price, A., Tolkovsky, A. M., & Brown, G. C. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003600 · Cited by 373 · see citing works
Genome-wide pleiotropy between Parkinson disease and autoimmune diseases
Witoelar, A., Jansen, I. E., Wang, Y., Desikan, R. S., Gibbs, J. R., Blauwendraat, C., Thompson, W. K., Hernandez, D. G., Djurovic, S., Schork, A. J., et al. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.0469 · Cited by 352 · see citing works
Local Genetic Correlation Gives Insights into the Shared Genetic Architecture of Complex Traits
Shi, H., Mancuso, N., Spendlove, S. J., & Paşaniuc, B. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.09.022 · Cited by 345 · see citing works
A Genome-Wide Meta-Analysis of Six Type 1 Diabetes Cohorts Identifies Multiple Associated Loci
Bradfield, J. P., Qu, H., Wang, K., Zhang, H., Abou‐Sleiman, P. M., Kim, C. E., Mentch, F. D., Qiu, H., Glessner, J., Thomas, K., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002293 · Cited by 338 · see citing works
Immune-mediated Mechanisms in the Pathoprogression of Amyotrophic Lateral Sclerosis
Zhao, W., Beers, D. R., & Appel, S. H. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9489-x · Cited by 298 · see citing works
Schork, A. J., Thompson, W. K., Pham, P., Torkamani, A., Roddey, J. C., Sullivan, P. F., Kelsoe, J. R., O’Donovan, M. C., Furberg, H., Schork, N. J., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003449 · Cited by 275 · see citing works
Loss-of-function mutations in the <i>C9ORF72</i> mouse ortholog cause fatal autoimmune disease
Burberry, A., Suzuki, N., Wang, J.-Y., Moccia, R., Mordes, D. A., Stewart, M. H., Suzuki-Uematsu, S., Ghosh, S., Singh, A., Merkle, F. T., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf6038 · Cited by 269 · see citing works
Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study
Shrine, N. R. G., Portelli, M. A., John, C., Artigas, M. S., Bennett, N., Hall, R., Lewis, J., Henry, A. P., Billington, C. K., Ahmad, A., et al. (2018) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(18)30389-8 · Cited by 244 · see citing works
Rab GTPases and Membrane Trafficking in Neurodegeneration
Kiral, F. R., Kohrs, F. E., Jin, E. J., & Hiesinger, P. R. (2018) · Current Biology · doi:10.1016/j.cub.2018.02.010 · Cited by 239 · see citing works
Crohn’s disease: NOD2, autophagy and ER stress converge
Fritz, T., Niederreiter, L., Adolph, T., Blumberg, R., & Kaser, A. (2011) · Gut · doi:10.1136/gut.2009.206466 · Cited by 236 · see citing works
Kuo, J. J., Siddique, T., Fu, R., & Heckman, C. J. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2004.074138 · Cited by 225 · see citing works
Lu, Q., Li, B., Ou, D., Erlendsdottir, M., Powles, R. L., Jiang, T., Hu, Y., Chang, D., Jin, C., Dai, W., et al. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.11.001 · Cited by 218 · see citing works
Neurologic and Psychiatric Manifestations of Celiac Disease and Gluten Sensitivity
Jackson, J. R., Eaton, W. W., Cascella, N. G., Fasano, A., & Kelly, D. L. (2011) · Psychiatric Quarterly · doi:10.1007/s11126-011-9186-y · Cited by 207 · see citing works
Autoimmune disease preceding amyotrophic lateral sclerosis: An epidemiologic study
Turner, M. R., Goldacre, R., Ramagopalan, S., Talbot, K., & Goldacre, M. J. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a6cc13 · Cited by 185 · see citing works
Characterization of Gene Expression Phenotype in Amyotrophic Lateral Sclerosis Monocytes
Zhao, W., Beers, D. R., Hooten, K. G., Sieglaff, D. H., Zhang, A., Sundaram, S. K., Traini, C., Halsey, W. S., Hughes, A. M., Sathe, G. M., et al. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2017.0357 · Cited by 176 · see citing works
Association between genetic traits for immune-mediated diseases and Alzheimer disease
Yokoyama, J. S., Wang, Y., Schork, A. J., Thompson, W. K., Karch, C. M., Cruchaga, C., McEvoy, L. K., Witoelar, A., Chen, C.-H., Holland, D., et al. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.0150 · Cited by 176 · see citing works
Depletion of reduced glutathione enhances motor neuron degeneration in vitro and in vivo
Chi, L., Ke, Y., Luo, C. T., Gozal, D., & Liu, R. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.09.064 · Cited by 167 · see citing works
Aoki, Y., Manzano, R., Lee, Y., Dafinca, R., Aoki, M., Douglas, A. G. L., Varela, M. A., Sathyaprakash, C., Scaber, J., Barbagallo, P., et al. (2017) · Brain · doi:10.1093/brain/awx024 · Cited by 159 · see citing works
Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study
Kioumourtzoglou, M.-A., Rotem, R. S., Seals, R. M., Gredal, O., Hansen, J., & Weisskopf, M. G. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.0910 · Cited by 145 · see citing works
Neuroinflammatory mechanisms in amyotrophic lateral sclerosis pathogenesis
Thonhoff, J. R., Simpson, E. P., & Appel, S. H. (2018) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000599 · Cited by 133 · see citing works
ATXN2 trinucleotide repeat length correlates with risk of ALS
Sproviero, W., Shatunov, A., Stahl, D. R., Shoai, M., van Rheenen, W., Jones, A. R., Al‐Sarraj, S., Andersen, P. M., Bonini, N. M., Conforti, F. L., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.11.010 · Cited by 131 · see citing works
Redox metals homeostasis in multiple sclerosis and amyotrophic lateral sclerosis: a review
Sheykhansari, S., Kozielski, K., Bill, J., Sitti, M., Gemmati, D., Zamboni, P., & Singh, A. V. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0379-2 · Cited by 120 · see citing works
Association between diabetes and amyotrophic lateral sclerosis in <scp>S</scp>weden
Mariosa, D., Kamel, F., Bellocco, R., Ye, W., & Fang, F. (2015) · European Journal of Neurology · doi:10.1111/ene.12632 · Cited by 120 · see citing works
The Gut-Brain Axis in Neurodegenerative Diseases and Relevance of the Canine Model: A Review
Ambrosini, Y. M., Borcherding, D. C., Kanthasamy, A., Kim, H. J., Willette, A., Jergens, A., Allenspach, K., & Mochel, J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00130 · Cited by 116 · see citing works
Benyamin, B., He, J., Zhao, Q., Gratten, J., Garton, F. C., Leo, P. J., Liu, Z., Mangelsdorf, M., Al‐Chalabi, A., Anderson, L. K., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00471-1 · Cited by 107 · see citing works
Inflammatory bowel disease and celiac disease: Overlaps and differences
Pascual, V. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i17.4846 · Cited by 105 · see citing works
Association of Long ATXN2 CAG Repeat Sizes With Increased Risk of Amyotrophic Lateral Sclerosis
Daoud, H., Belzil, V., Martins, S., Sabbagh, M., Provencher, P., Lacomblez, L., Meininger, V., Camu, W., Dupré, N., Dion, P. A., et al. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.111 · Cited by 103 · see citing works
Increased prevalence of autoimmune disease within C9 and FTD/MND cohorts: Completing the picture
Miller, Z. A., Sturm, V. E., Camsari, G. B., Karydas, A., Yokoyama, J. S., Grinberg, L. T., Boxer, A. L., Rosen, H. J., Rankin, K. P., Gorno-Tempini, M. L., et al. (2016) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000000301 · Cited by 100 · see citing works
Zeng, P., Wang, T., Zheng, J., & Zhou, X. (2019) · BMC Medicine · doi:10.1186/s12916-019-1448-9 · Cited by 96 · see citing works
Mutant SOD 1 inhibits ER ‐Golgi transport in amyotrophic lateral sclerosis
Atkin, J. D., Farg, M. A., Soo, K. Y., Walker, A. K., Halloran, M. A., Turner, B. J., Nagley, P., & Horne, M. K. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12493 · Cited by 78 · see citing works
Membrane trafficking in neuronal maintenance and degeneration
Wang, D., Chan, C., Cherry, S., & Hiesinger, P. R. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1201-4 · Cited by 72 · see citing works
Sundaramoorthy, V., Sultana, J. M., & Atkin, J. D. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00400 · Cited by 72 · see citing works
Tamura, N., Kuwabara, S., Misawa, S., Kanai, K., Nakata, M., Sawai, S., & Hattori, T. (2006) · Clinical Neurophysiology · doi:10.1016/j.clinph.2006.07.309 · Cited by 66 · see citing works
Autoimmunity in Amyotrophic Lateral Sclerosis: Past and Present
Pagani, M. R., Gonzalez, L. E., & Uchitel, O. D. (2011) · Neurology Research International · doi:10.1155/2011/497080 · Cited by 59 · see citing works
Ionic Homeostasis Maintenance in ALS: Focus on New Therapeutic Targets
Sirabella, R., Valsecchi, V., Anzilotti, S., Cuomo, O., Vinciguerra, A., Cepparulo, P., Brancaccio, P., Guida, N., Blondeau, N., Canzoniero, L. M. T., et al. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00510 · Cited by 59 · see citing works
Are the inflammatory bowel diseases autoimmune disorders?
Snook, J. A. (1990) · Gut · doi:10.1136/gut.31.9.961 · Cited by 57 · see citing works
Population-based risks for cancer in patients with ALS
Gibson, S. B., Abbott, D., Farnham, J. M., Thai, K. K., McLean, H., Figueroa, K. P., Bromberg, M. B., Pulst, S. M., & Cannon‐Albright, L. (2016) · Neurology · doi:10.1212/wnl.0000000000002757 · Cited by 53 · see citing works
Gut microbes augment neurodegeneration
Erny, D., & Prinz, M. (2017) · Nature · doi:10.1038/nature21910 · Cited by 45 · see citing works
Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral Sclerosis
Gadoth, A., Nefussy, B., Bleiberg, M., Klein, T., Artman, I., & Drory, V. E. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.48 · Cited by 44 · see citing works
ITIH4 and Gpx3 are potential biomarkers for amyotrophic lateral sclerosis
Tanaka, H., Shimazawa, M., Takata, M., Kaneko, H., Tsuruma, K., Ikeda, T., Warita, H., Aoki, M., Yamada, M., Takahashi, H., et al. (2013) · Journal of Neurology · doi:10.1007/s00415-013-6877-3 · Cited by 37 · see citing works
Du, Y., Wen, Y. F., Guo, X., Hao, J., Wang, W., He, A., Fan, Q., Li, P., Liu, L., Liang, X., et al. (2017) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-017-0512-2 · Cited by 34 · see citing works
Effects of diabetes mellitus on amyotrophic lateral sclerosis: a systematic review
Lekoubou, A., Matsha, T. E., Sobngwi, E., & Kengne, A. P. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-171 · Cited by 34 · see citing works
Zeng, L., Zhang, D., McLoughlin, H. S., Zalon, A. J., Aravind, L., & Paulson, H. L. (2018) · PLoS ONE · doi:10.1371/journal.pone.0204438 · Cited by 34 · see citing works
Fredi, M., Cavazzana, I., Biasiotto, G., Filosto, M., Padovani, A., Monti, E., Tincani, A., Franceschini, F., & Zanella, I. (2019) · NeuroMolecular Medicine · doi:10.1007/s12017-019-08528-8 · Cited by 29 · see citing works
GGNBP2 acts as a tumor suppressor by inhibiting estrogen receptor α activity in breast cancer cells
Lan, Z., Hu, Y.-H., Zhang, S., Li, X., Zhou, H., Ding, J., Klinge, C. M., Radde, B. N., Cooney, A. J., Zhang, J., et al. (2016) · Breast Cancer Research and Treatment · doi:10.1007/s10549-016-3880-2 · Cited by 23 · see citing works
No association between gluten sensitivity and amyotrophic lateral sclerosis
Visser, A. E., Pazoki, R., Pulit, S. L., van Rheenen, W., Raaphorst, J., van der Kooi, A. J., Ricaño-Ponce, I., Wijmenga, C., Otten, H. G., Veldink, J. H., et al. (2017) · Journal of Neurology · doi:10.1007/s00415-017-8400-8 · Cited by 12 · see citing works
Piątek-Guziewicz, A., Zagrodzki, P., Paśko, P., Krośniak, M., Ptak‐Belowska, A., Przybylska-Feluś, M., Mach, T., & Zwolinska-Wcislo, M. M. (2017) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.4020 · Cited by 11 · see citing works
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Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
“A genome-wide association study also demonstrated a specific genetic correlation between ALS and autoimmune diseases.(87) Therefore, inflammation should have close relationship with the development of ALS.”
BackgroundEtiology, effects and management of comorbidities in multiple sclerosis: recent advances
Marrie, R. A., Fisk, J. D., Fitzgerald, K. C., Kowalec, K., Maxwell, C. J., Rotstein, D., Salter, A. R., & Tremlett, H. L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1197195 · Cited by 115 · see citing works
Ziff, O. J., Clarke, B. E., Taha, D. M., Crerar, H., Luscombe, N. M., & Patani, R. (2021) · Genome Research · doi:10.1101/gr.275939.121 · Cited by 91 · see citing works
Yang, X., Li, G., Lou, P., Zhang, M., Yao, K., Xiao, J., Chen, Y., Xu, J., Tian, S., Deng, M., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2307395120 · Cited by 48 · see citing works
Firdaus, Z., & Li, X. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042320 · Cited by 43 · see citing works
The toxic metal hypothesis for neurological disorders
Pamphlett, R., & Bishop, D. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1173779 · Cited by 39 · see citing works
Anderson, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043300 · Cited by 34 · see citing works
Emerging Trends in the Field of Inflammation and Proteinopathy in ALS/FTD Spectrum Disorder
Marchi, F. D., Franjkic, T., Schito, P., Russo, T., Nimac, J., Chami, A. A., Mele, A., Vidatic, L., Križ, J., Julien, J., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11061599 · Cited by 28 · see citing works
Zhang, J., Zhang, S., Qiao, J., Wang, T., & Zeng, P. (2023) · BMC Genomics · doi:10.1186/s12864-023-09434-x · Cited by 31 · see citing works
Daniela Gerovska, D., & Araúzo-Bravo, M. J. (2023) · Cells · doi:10.3390/cells12071061 · Cited by 28 · see citing works
Shared genetic links between frontotemporal dementia and psychiatric disorders
Li, C., Pang, D., Lin, J., Yang, T., & Shang, H. (2022) · BMC Medicine · doi:10.1186/s12916-022-02335-y · Cited by 26 · see citing works
Self-citationMegagiannis, P., Yuan, M., Yan, R., Yuan, L., Wilde, J. J., Eckersberg, H., Suresh, R., Tan, X., Chen, H., Farmer, W. T., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114637 · Cited by 26 · see citing works
Alipour, P., Senkevich, K. A., Ross, J. P., Spiegelman, D., Manousaki, D., Dion, P. A., & Rouleau, G. A. (2022) · BMC Medicine · doi:10.1186/s12916-022-02578-9 · Cited by 25 · see citing works
Guo, R., Chen, Y., Zhang, J., Zhou, Z., Feng, B., Du, X., Liu, X., Ma, J., & Cui, H. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03836-4 · Cited by 23 · see citing works
Immunogenetic Determinants of Parkinson’s Disease Etiology
Kung, P., Elsayed, I., Reyes‐Pérez, P., & Bandrés‐Ciga, S. (2022) · Journal of Parkinson s Disease · doi:10.3233/jpd-223176 · Cited by 19 · see citing works
Effects of exercise on neuroinflammation in age-related neurodegenerative disorders
Su, Y., & Su, Z. (2025) · European journal of medical research · doi:10.1186/s40001-025-03165-3 · Cited by 18 · see citing works
C9orf72 Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age
Zanella, I., Zacchi, E., Piva, S., Filosto, M., Beligni, G., Alaverdian, D. A., Amitrano, S., Fava, F., Baldassarri, M., Frullanti, E., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136991 · Cited by 14 · see citing works
Modeling ALS with Patient-Derived iPSCs: Recent Advances and Future Potentials
Nejad, L. D., & Pioro, E. P. (2025) · Brain Sciences · doi:10.3390/brainsci15020134 · Cited by 12 · see citing works
Nowowiejska, J., Baran, A. M., Hermanowicz, J. M., Sieklucka, B., Krahel, J. A., Kiluk, P., Pawlak, D., & Flisiak, I. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11092430 · Cited by 12 · see citing works
Aberrant protein aggregation in amyotrophic lateral sclerosis
Wang, H., & Zeng, R. (2024) · Journal of Neurology · doi:10.1007/s00415-024-12485-z · Cited by 11 · see citing works
Psoriasis and neurodegenerative diseases—a review
Nowowiejska, J., Baran, A. M., & Flisiak, I. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.917751 · Cited by 10 · see citing works
GGNBP2 regulates MDA5 sensing triggered by self double-stranded RNA following loss of ADAR1 editing
Heraud-Farlow, J. E., Taylor, S., Chalk, A. M., Escudero, A., Hu, S.-B., Goradia, A., Sun, T., Li, Q., Nikolić, I., Li, J. B., et al. (2024) · Science Immunology · doi:10.1126/sciimmunol.adk0412 · Cited by 10 · see citing works
Xiao, Y., Wei, Q., Ou, R., Yang, T., Jiang, Q., Hou, Y., Zhang, L., Liu, K., Wang, S., Lin, J., et al. (2023) · Journal of Neurology · doi:10.1007/s00415-023-11790-3 · Cited by 9 · see citing works
Self-citationEck, R. J., Stair, J. G., Kraemer, B. C., & Liachko, N. F. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1300705 · Cited by 9 · see citing works
Pastrana, C. I., González, F. J. N., Macrì, M., Martínez, A. M., Ciani, E., & Bermejo, J. V. D. (2024) · BMC Veterinary Research · doi:10.1186/s12917-024-04263-w · Cited by 8 · see citing works
Li, S., Zhang, Q., Li, J., & Weng, L. (2022) · The EPMA Journal · doi:10.1007/s13167-022-00299-w · Cited by 7 · see citing works
C9orf72 Alleviates DSS‑Induced Ulcerative Colitis via the cGAS‐STING Pathway
Wang, Y., Xu, T., & Wang, W. (2025) · Immunity Inflammation and Disease · doi:10.1002/iid3.70139 · Cited by 6 · see citing works
Drug repurposing candidates for amyotrophic lateral sclerosis using common and rare genetic variants
Gerring, Z. F., Bhalala, O. G., Fearnley, L. G., Oikari, L. E., White, A. R., Derks, E. M., Watson, R., Yassi, N., Bahlo, M., & Reay, W. R. (2025) · Brain Communications · doi:10.1093/braincomms/fcaf184 · Cited by 6 · see citing works
Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases
Shen, R., Sung, K., Ding, J., & Wu, C. (2026) · Translational Neurodegeneration · doi:10.1186/s40035-026-00543-7 · Cited by 6 · see citing works
The Role of Genetics on Psoriasis Susceptibility, Comorbidities, and Treatment Response
Bui, A., Orcales, F., Kranyak, A. C., Chung, B. Y., Haran, K., Smith, P. L., Johnson, C. E., & Liao, W. J. (2024) · Dermatologic Clinics · doi:10.1016/j.det.2024.02.005 · Cited by 6 · see citing works
Disease-specific prioritization of non-coding GWAS variants based on chromatin accessibility
Liang, Q., Abraham, A., Capra, J. A., & Kostka, D. (2024) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2024.100310 · Cited by 5 · see citing works
Clinical characteristics and prognosis of amyotrophic lateral sclerosis with autoimmune diseases
Li, J.-Y., Sun, X., Shen, D., Yang, X., Liu, M., & Cui, L. (2022) · PLoS ONE · doi:10.1371/journal.pone.0266529 · Cited by 5 · see citing works
Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS
Vasilopoulou, C., McDaid-McCloskey, S. L., McCluskey, G., Duguez, S., Morris, A. P., & Duddy, W. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24044021 · Cited by 4 · see citing works
Xiong, J., Chen, X., Huang, K., & Pan, Y. (2025) · Clinical Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s505143 · Cited by 3 · see citing works
Dysregulation of Gene Expressions in Multiple Sclerosis: TNFSF13B and Other Candidate Genes
Consiglio, A., Nuzziello, N., & Liguori, M. (2022) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2201004 · Cited by 3 · see citing works
Silva, J. F. (2024) · American Journal of Translational Research · doi:10.62347/owyy4960 · Cited by 2 · see citing works
Cao, W., Cao, Z., Tang, L., Xu, C., & Fan, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1356132 · Cited by 2 · see citing works
Mutation Screening of ATXN1, ATXN2, and ATXN3 in Amyotrophic Lateral Sclerosis
Yang, T., Wei, Q., Pang, D., Cheng, Y., Huang, J., Lin, J., Xiao, Y., Jiang, Q., Wang, S., Li, C., et al. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04600-y · Cited by 2 · see citing works
Self-citationLuo, Q., An, M., Wu, Y., Wang, J., Mao, Y., Zhang, L., & Wang, C. (2024) · Archives of Dermatological Research · doi:10.1007/s00403-024-03617-6 · Cited by 2 · see citing works
Jellinger, K. A. (2025) · Journal of Neural Transmission · doi:10.1007/s00702-025-02975-3 · Cited by 2 · see citing works
Prevalence and impact of comorbidities in amyotrophic lateral sclerosis
Jellinger, K. A. (2025) · Journal of Neural Transmission · doi:10.1007/s00702-025-02971-7 · Cited by 1 · see citing works
Frolov, A., D'sa, E., Henderson, C., Guzmán, M. A., Hayat, G. R., & Martin, J. R. (2024) · Cureus · doi:10.7759/cureus.76027 · Cited by 1 · see citing works
Tuberculin responses after BCG vaccination predict amyotrophic lateral sclerosis risk
Nakken, O., Vaage, A. M., Stigum, H., Heldal, E., Meyer, H. E., & Holmøy, T. (2023) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2023.100704
Zhang, J., Zhang, S., Qiao, J., Wang, T., & Zeng, P. (2023) · Figshare · doi:10.6084/m9.figshare.23505076
The Prevalence of Various Autoimmune Comorbidities in Patients with Inflammatory Bowel Disease
Singh, B., Kalra, S., Khanna, T., Kohli, I., Kumar, V., Sohal, A., & Sejpal, D. V. (2025) · Epidemiologia · doi:10.3390/epidemiologia6030052
A Case of Amyotrophic Lateral Sclerosis With Coexisting Maturity-onset Diabetes of the Young Type 5
Tanaka, S., Kobayashi, M., Ikeguchi, R., & Iwasaki, N. (2025) · JCEM Case Reports · doi:10.1210/jcemcr/luaf219
Li, L. J., Xu, F., Duan, H., Qi, J., Zhang, J., & Ma, K. (2025) · European journal of medical research · doi:10.1186/s40001-025-03335-3
Zhang, J., Zhang, S., Qiao, J., Wang, T., & Zeng, P. (2023) · Figshare · doi:10.6084/m9.figshare.23505079
A scoping review of comorbidity aetiology in multiple sclerosis
Safa, M., Riel, H., Krysak, M., Hejazi, M., Cardwell, K., Marrie, R. A., & Kowalec, K. (2026) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2026.107382
- Authors
- Li, C. Y., Yang, T. M., Ou, R. W., Wei, Q. Q., & Shang, H. F.
- Affiliations
- Sichuan University (CN)
- Corresponding author
- Shang, Hui Fang
- Venue
- BMC Medicine
- Published
- 2021-02-05
- Volume
- 19
- Issue
- 1
- Pages
- 27-27
- ISSN
- 1741-7015 (ISSN-L)
- PMC
- PMC7863260
- OpenAlex
- W3128131872
- Cited by
- 48
- References
- 80
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 13 · 2023: 13 · 2022: 8 · 2021: 2
- FWCI
- 4.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- the National Natural Science Foundation of China (81901294)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- amyotrophic lateral sclerosis, autoimmune disease, genetic correlation, shared genetic risk loci, pleiotropy, celiac disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, ulcerative colitis, type 1 diabetes, psoriasis, glutathione peroxidase 3, C9orf72, ataxin-3, membrane trafficking, ER-Golgi transport, genetic enrichment
- MeSH terms
- Amyotrophic Lateral Sclerosis, Arthritis, Rheumatoid, Autoimmune Diseases, Celiac Disease, Colitis, Ulcerative, Crohn Disease, Diabetes Mellitus, Type 1, Humans, Lupus Erythematosus, Systemic, Multiple Sclerosis, Psoriasis, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study
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