Susceptible genes and disease mechanisms identified in frontotemporal dementia and frontotemporal dementia with Amyotrophic Lateral Sclerosis by DNA-methylation and GWAS
| Autor: | Taskesen, E, Mishra, A, van der Sluis, S, Ferrari, R, Veldink, Jh, van Es MA4, Smit, Ab5, Posthuma, D1, 2, Hernandez DG, Pijnenburg Y., Nalls, Ma, Rohrer, Jd, Ramasamy, A, Kwok, Jbj, Dobson-Stone, C, Schofield, Pr, Halliday, Gm, Hodges, Jr, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, Nj, Benussi, L, Binetti, G, Ghidoni, Roberta, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, Ml, Nilsson, K, Nilsson, C, Mackenzie, Ira, Hsiung, Gr, Mann, Dma, Grafman, J, Morris, Cm, Attems, J, Griffiths, Td, Mckeith, Ig, Thomas, Aj, Pietrini, P, Huey, Ed, Wassermann, Em, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, George-Hyslop, Ps, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, Jb, Schlachetzki, Jcm, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin VM, Grossman, M, Trojanowski, Jq, van der Zee, J, Van Broeckhoven, C, Cappa, Sf, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, Je, Hjermind, Le, Riemenschneider, GUNNAR MARKUS, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, Mn, Fox, Nc, Warren, Jd, Spillantini, Mg, Morris, Hr, Rizzu, P, Heutink, P, Snowden, Js, Rollinson, S, Richardson, A, Gerhard, A, Bruni, Ac, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, Lara, Anfossi, M, Gallo, M, Conidi, Me, Smirne, N, Rademakers, R, Baker, M, Dickson, Dw, Graff-Radford, Nr, Petersen, Rc, Knopman, D, Josephs, Ka, Boeve, Bf, Parisi, Je, Seeley, Ww, Miller, Bl, Karydas, Am, Rosen, H, van Swieten JC, Dopper, Egp, Seelaar, H, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, Aa, Franceschi, M, Postiglione, Antonio, Milan, Gian Luca, Sorrentino, Paolo Luigi, Kristiansen, M, Chiang, Hh, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, Ab, Hardy, J, Momeni, P. |
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| Přispěvatelé: | Rademakers, Rosa, International FTD-Genomics Consortium, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience - Neurodegeneration, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Human genetics, APH - Quality of Care, Midwifery Science, Divisions, Neurology, Amsterdam Reproduction & Development (AR&D), Mishra, A [0000-0002-8141-1543], van der Sluis, S [0000-0001-9958-7216], van Es, MA [0000-0002-7709-5883], Posthuma, D [0000-0001-7582-2365], Apollo - University of Cambridge Repository |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Candidate gene Science Genome-wide association study Biology Neurodegenerative Article 03 medical and health sciences 0302 clinical medicine Rare Diseases SDG 3 - Good Health and Well-being mental disorders medicine Journal Article Acquired Cognitive Impairment Genetics 2.1 Biological and endogenous factors Amyotrophic lateral sclerosis Aetiology General Alzheimer's Disease Related Dementias (ADRD) Genetic association Multidisciplinary Genetic heterogeneity International FTD-Genomics Consortium Neurodegeneration Human Genome Neurosciences nutritional and metabolic diseases Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) medicine.disease nervous system diseases Brain Disorders Frontotemporal Dementia (FTD) 030104 developmental biology DNA methylation Neurological Medicine Dementia Human medicine ALS 030217 neurology & neurosurgery Frontotemporal dementia |
| Zdroj: | Scientific reports, vol 7, iss 1 Taskesen, E, Mishra, A, van der Sluis, S, Ferrari, R, Veldink, J H, van Es, M A, Smit, A B, Posthuma, D & Pijnenburg, Y 2017, ' Susceptible genes and disease mechanisms identified in frontotemporal dementia and frontotemporal dementia with Amyotrophic Lateral Sclerosis by DNA-methylation and GWAS ', Scientific Reports, vol. 7, no. 1, 8899, pp. 8899 . https://doi.org/10.1038/s41598-017-09320-z Scientific reports Scientific Reports, 7(1):8899. Nature Publishing Group Scientific Reports, 7(1). Nature Publishing Group Scientific Reports Taskesen, E, Mishra, A K, Van Der Sluis, S, Ferrari, R, Veldink, J H, Van Es, M A, Smit, A B, Posthuma, D & Pijnenburg, Y 2017, ' Susceptible genes and disease mechanisms identified in frontotemporal dementia and frontotemporal dementia with Amyotrophic Lateral Sclerosis by DNA-methylation and GWAS ', Scientific Reports, vol. 7, no. 1, 8899 . https://doi.org/10.1038/s41598-017-09320-z Scientific Reports, Vol 7, Iss 1, Pp 1-16 (2017) |
| ISSN: | 2045-2322 |
| Popis: | Frontotemporal dementia (FTD) is a neurodegenerative disorder predominantly affecting the frontal and temporal lobes. Genome-wide association studies (GWAS) on FTD identified only a few risk loci. One of the possible explanations is that FTD is clinically, pathologically, and genetically heterogeneous. An important open question is to what extent epigenetic factors contribute to FTD and whether these factors vary between FTD clinical subgroup. We compared the DNA-methylation levels of FTD cases (n = 128), and of FTD cases with Amyotrophic Lateral Sclerosis (FTD-ALS; n = 7) to those of unaffected controls (n = 193), which resulted in 14 and 224 candidate genes, respectively. Cluster analysis revealed significant class separation of FTD-ALS from controls. We could further specify genes with increased susceptibility for abnormal gene-transcript behavior by jointly analyzing DNA-methylation levels with the presence of mutations in a GWAS FTD-cohort. For FTD-ALS, this resulted in 9 potential candidate genes, whereas for FTD we detected 1 candidate gene (ELP2). Independent validation-sets confirmed the genes DLG1, METTL7A, KIAA1147, IGHMBP2, PCNX, UBTD2, WDR35, and ELP2/SLC39A6 among others. We could furthermore demonstrate that genes harboring mutations and/or displaying differential DNA-methylation, are involved in common pathways, and may therefore be critical for neurodegeneration in both FTD and FTD-ALS. |
| Databáze: | OpenAIRE |
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