Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies
| Title: | Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies |
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| Authors: | Broce I1; Karch CM2; Wen N2; Fan CC3; Wang Y4; 5; Tan CH1; Kouri N6; Ross OA6; Höglinger GU7; 8 9; Muller U10; Hardy J11; International FTD-Genomics Consortium; Momeni P12; Hess CP1; Dillon WP1; Miller ZA13; Bonham LW13; Rabinovici GD13; Rosen HJ13; Schellenberg GD14; Franke A15; Karlsen TH16; 17 18; Veldink JH19; Ferrari R11; Yokoyama JS13; Miller BL13; Andreassen OA4; Dale AM3; 20 21; Desikan RS1; 13; Sugrue LP1. Collaborators (158) Ferrari R; Hernandez DG; Nalls MA; Rohrer JD; Ramasamy A; Kwok JBJ; Dobson-Stone C; Brooks WS; 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 R; Forloni G; Galimberti D; Fenoglio C; Serpente M; Scarpini E; Clarimón J; Lleó A; Blesa R; Waldö ML; Nilsson K; Nilsson C; Mackenzie IRA; Hsuing GYR; Mann DMA; Grafman J; Morris CM; Attems J; Griffiths TD; McKeith IG; Thomas AJ; Pietrini P; Huey ED; Wasserman EM; Baborie A; Jaros E; Tierney MC; Pastor P; Razquin C; Ortega-Cubero S; Alonso E; Perneczky E; Diehl-Schmid J; Alexopoulos P; Kurz A; Rainero I; Rubino E; Pinessi L; Rogaeva E; St George-Hyslop P; Rossi G; Tagliavini F; Giaccone G; Rowe JB; Schlachetzki JCM; Uphill J; Collinge J; Mead S; Danek A; Van Deerlin VM; Grossmann M; Trojanowski JQ; van der Zee J; Deschamps W; Van Langenhove T; Cruts M; Van Broeckhoven C; Cappa SF; Le Ber I; Hannequin D; Golfier V; Vercelletto M; Brice A; Nacimas B; Sorbi S; Bagnoli S; Piaceri I; Nielsen JE; Hjermind LE; Riemenschneider M; Mayhaus M; Ibach B; Gasparoni G; Pichler S; Gu W; Rossor MN; Fox NC; Warren JD; Spillantini MG; Morris HR; Rizzu P; Heutnik P; Snowden J; Rollinson S; Richardson A; Gerhard A; Bruni AC; Maletta R; Frangipane F; Cupidi C; Bernardi L; Anfossi M; Gallo M; Conidi ME; Smirne N; Rademakers R; Baker M; Dickson DW; Graff-Radford NR; Peterson RC; Knopman D; Josephs KA; Boeve BF; Parisi JE; Seeley WW; Miller BL; Karydas AM; Rosen H; van Swieten JC; Dopper EGP; Seelaar H; Pijnenburg YAL; Scheltens P; Logroscino G; Capozzo R; Novelli V; Puca AA; Franceschi M; Postiglione A; Milan G; Sorrentino P; Kristiansen M; Chiang HH; Graff C; Pasquier F; Rollin A; Deramecourt V; Lebert F; Kapogiannis D; Ferucci L; Pickering-Brown S; Singleton AB; Hardy J; Momeni P. |
| Contributors: | Broce, I1; Karch, Cm2; Wen, N2; Fan, Cc3; Wang, Y4; 5; Tan, Ch1; Kouri, N6; Ross, Oa6; Höglinger, Gu7; 8, 9; Muller, U10; Hardy, J11; International FTD-Genomics, Consortium; Momeni, P12; Hess, Cp1; Dillon, Wp1; Miller, Za13; Bonham, Lw13; Rabinovici, Gd13; Rosen, Hj13; Schellenberg, Gd14; Franke, A15; Karlsen, Th16; 17, 18; Veldink, Jh19; Ferrari, R11; Yokoyama, Js13; Miller, Bl13; Andreassen, Oa4; Dale, Am3; 20, 21; Desikan, Rs1; 13; Sugrue LP1., Collaborators (158) Ferrari R; Hernandez, Dg; Nalls, Ma; Rohrer, Jd; Ramasamy, A; Kwok, Jbj; Dobson-Stone, C; Brooks, W; 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, R; Forloni, G; Galimberti, D; Fenoglio, C; Serpente, M; Scarpini, E; Clarimón, J; Lleó, A; Blesa, R; Waldö, Ml; Nilsson, K; Nilsson, C; Mackenzie, Ira; Hsuing, Gyr; Mann, Dma; Grafman, J; Morris, Cm; Attems, J; Griffiths, Td; Mckeith, Ig; Thomas, Aj; Pietrini, P; Huey, Ed; Wasserman, Em; Baborie, A; Jaros, E; Tierney, Mc; Pastor, P; Razquin, C; Ortega-Cubero, S; Alonso, E; Perneczky, E; Diehl-Schmid, J; Alexopoulos, P; Kurz, A; Rainero, I; Rubino, E; Pinessi, L; Rogaeva, E; St George-Hyslop, P; Rossi, G |
| Publication Year: | 2018 |
| Collection: | Archivio della ricerca della Scuola IMT Alti Studi Lucca |
| Subject Terms: | Frontal lobe dementia; Pleiotropy; Gnetic |
| Description: | BACKGROUND:Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed.METHODS AND FINDINGS:Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate < 0.05 and after excluding SNPs in linkage disequilibrium, we found that 8 of the 15 identified loci mapped to the human leukocyte antigen (HLA) region on Chromosome (Chr) 6. We also found novel candidate FTD susceptibility loci within LRRK2 (leucine rich repeat kinase 2), TBKBP1 (TBK1 binding protein 1), and PGBD5 (piggyBac transposable element derived 5). ... |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/29315334; journal:PLOS MEDICINE; https://hdl.handle.net/20.500.11771/3572; http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002487 |
| DOI: | 10.1371/journal.pmed.1002487 |
| Availability: | https://hdl.handle.net/20.500.11771/3572; https://doi.org/10.1371/journal.pmed.1002487; http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002487 |
| Rights: | info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc-nd/3.0/it/ |
| Accession Number: | edsbas.1F8FFC3F |
| Database: | BASE |