Selective Genetic Overlap Between Amyotrophic Lateral Sclerosis and Diseases of the Frontotemporal Dementia Spectrum
| العنوان: | Selective Genetic Overlap Between Amyotrophic Lateral Sclerosis and Diseases of the Frontotemporal Dementia Spectrum |
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| المؤلفون: | Karch, Cm, Wen, N, Fan, Cc2, Yokoyama, Js, Kouri, N, Ross, Oa, Höglinger, G, Müller, U, Ferrari, R, Hardy, J, Schellenberg, Gd, Sleiman, Pm, Momeni, P, Hess, Cp, Miller, Bl, Sharma, M, Van Deerlin, V, Smeland, Ob, Andreassen, Oa, Dale, Am, Desikan, Rs, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Ekaterina Rogaeva, Peter St George-Hyslop, Giacomina, Rossi, Fabrizio Tagliavini, Giorgio, Giaccone |
| المصدر: | JAMA neurology 75(7), 860 (2018). doi:10.1001/jamaneurol.2018.0372 JAMA neurology, vol 75, iss 7 |
| بيانات النشر: | American Medical Association, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Aging, ERGIC1 protein, human, genetics [Basal Ganglia Diseases], Vesicular Transport Proteins, Genome-wide association study, genetics [Alzheimer Disease], Disease, Neurodegenerative, 0302 clinical medicine, Superoxide Dismutase-1, Progressive Supranuclear Palsy (PSP) Genetics Consortium, C9orf72, genetics [Parkinson Disease], Corticobasal degeneration, 2.1 Biological and endogenous factors, Supranuclear Palsy, BNIP1 protein, human, Amyotrophic lateral sclerosis, Aetiology, genetics [Proto-Oncogene Proteins c-bcl-2], and International Parkinson’s Disease Genomics Consortium, genetics [Frontotemporal Dementia], genetics [Nerve Tissue Proteins], Genetics, genetics [Supranuclear Palsy, Progressive], SOD1 protein, human, Parkinson Disease, genetics [Superoxide Dismutase-1], genetics [Amyotrophic Lateral Sclerosis], Proto-Oncogene Proteins c-bcl-2, International Collaboration for Frontotemporal Dementia, Frontotemporal Dementia, Neurological, International Frontotemporal Dementia (FTD)–Genomics Consortium, Cognitive Sciences, Supranuclear Palsy, Progressive, Alzheimer's disease, Frontotemporal dementia, Clinical Sciences, MAPT protein, human, Nerve Tissue Proteins, tau Proteins, Article, Progressive supranuclear palsy, 03 medical and health sciences, Rare Diseases, Basal Ganglia Diseases, Progressive, genetics [Vesicular Transport Proteins], Alzheimer Disease, medicine, Acquired Cognitive Impairment, Humans, Genetic Predisposition to Disease, ddc:610, genetics [C9orf72 Protein], Neurology & Neurosurgery, UNC13B protein, human, C9orf72 Protein, business.industry, Amyotrophic Lateral Sclerosis, Neurosciences, genetics [TDP-43 Proteinopathies], Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, Brain Disorders, genetics [tau Proteins], 030104 developmental biology, TDP-43 Proteinopathies, Dementia, Neurology (clinical), ALS, C9orf72 protein, human, business, 030217 neurology & neurosurgery, Genome-Wide Association Study |
| الوصف: | Importance:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by loss of upper and lower motor neurons. Although novel ALS genetic variants have been identified, the shared genetic risk between ALS and other neurodegenerative disorders remains poorly understood. Objectives:To examine whether there are common genetic variants that determine the risk for ALS and other neurodegenerative diseases and to identify their functional pathways. Design, Setting, and Participants:In this study conducted from December 1, 2016, to August 1, 2017, the genetic overlap between ALS, sporadic frontotemporal dementia (FTD), FTD with TDP-43 inclusions, Parkinson disease (PD), Alzheimer disease (AD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP) were systematically investigated in 124 876 cases and controls. No participants were excluded from this study. Diagnoses were established using consensus criteria. Main Outcomes and Measures:The primary outcomes were a list of novel loci and their functional pathways in ALS, FTD, PSP, and ALS mouse models. Results:Among 124 876 cases and controls, genome-wide conjunction analyses of ALS, FTD, PD, AD, CBD, and PSP revealed significant genetic overlap between ALS and FTD at known ALS loci: rs13302855 and rs3849942 (nearest gene, C9orf72; P = .03 for rs13302855 and P = .005 for rs3849942) and rs4239633 (nearest gene, UNC13A; P = .03). Significant genetic overlap was also found between ALS and PSP at rs7224296, which tags the MAPT H1 haplotype (nearest gene, NSF; P = .045). Shared risk genes were enriched for pathways involving neuronal function and development. At a conditional FDR P |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e5144cd809c5ecbb53e7f59ac1e490cdTest https://pub.dzne.de/record/140070Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e5144cd809c5ecbb53e7f59ac1e490cd |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |