| Title: |
Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies |
| Authors: |
Broce, Iris; Karch, Celeste M.; Wen, Natalie; Fan, Chun C.; Wang, Yunpeng; Hong Tan, Chin; Kouri, Naomi; Ross, Owen A.; Höglinger, Günter U.; Muller, Ulrich; Hardy, John; Momeni, Parastoo; Hess, Christopher P.; Dillon, William P.; Miller, Zachary A.; Bonham, Luke W.; Rabinovici, Gil D.; Rosen, Howard J.; Schellenberg, Gerard D.; Franke, Andre; Karlsen, Tom H.; Veldink, Jan H.; Ferrari, Raffaele; Yokoyama, Jennifer S.; Miller, Bruce L.; Andreassen, Ole A.; Dale, Anders M.; Desikan, Rahul S.; Sugrue, Leo P.; Hernandez, Dena G.; Nalls, Michael A.; Rohrer, Jonathan D.; Ramasamy, Adaikalavan; Kwok, John B. J.; Dobson-Stone, Carol; Brooks, William S.; Schofield, Peter R.; Halliday, Glenda M.; Hodges, John R.; Piguet, Olivier; Bartley, Lauren; Thompson, Elizabeth; Haan, Eric; Hernández, Isabel; Ruiz, Agustín; Boada, Mercè; Borroni, Barbara; Padovani, Alessandro; Cruchaga, Carlos; Cairns, Nigel J.; Benussi, Luisa; Binetti, Giuliano; Ghidoni, Roberta; Forloni, Gianluigi; Albani, Diego; Galimberti, Daniela; Fenoglio, Chiara; Serpente, Maria; Scarpini, Elio; Clarimón, Jordi; Lleó, Alberto; Blesa, Rafael; Landqvist Waldö, Maria; Nilsson, Karin; Nilsson, Christer; Mackenzie, Ian R. A.; Hsiung, Ging-Yuek R.; Mann, David M. A.; Grafman, Jordan; Morris, Christopher M.; Attems, Johannes; Griffiths, Timothy D.; G McKeith, Ian; Thomas, Alan J.; Pietrini, Pietro; Huey, Edward D.; Wassermann, Eric M.; Baborie, Atik; Jaros, Evelyn; Tierney, Michael C.; Pastor, Pau; Razquin, Cristina; Ortega-Cubero, Sara; Alonso, Elena; Perneczky, Robert; Diehl-Schmid, Janine; Alexopoulos, Panagiotis; Kurz, Alexander; Rainero, Innocenzo; Rubino, Elisa; Pinessi, Lorenzo; Rogaeva, Ekaterina; St George-Hyslop, Peter; Rossi, Giacomina; Tagliavini, Fabrizio; Giaccone, Giorgio; Rowe, James B.; Schlachetzki, Johannes C. M.; Uphill, James; Collinge, John; Mead, Simon; Danek, Adrian; Van Deerlin, Vivianna M.; Grossman, Murray; Trojanowski, John Q.; van der Zee, Julie; Cruts, Marc; Broeckhoven, Christine Van; Cappa, Stefano F.; Leber, Isabelle; Hannequin, Didier; Golfier, Véronique; Vercelletto, Martine; Brice, Alexis; Nacmias, Benedetta; Sorbi, Sandro; Bagnoli, Silvia; Piaceri, Irene; Nielsen, Jørgen E.; Hjermind, Lena E.; Riemenschneider, Matthias; Mayhaus, Manuel; Ibach, Bernd; Gasparoni, Gilles; Pichler, Sabrina; Gu, Wei; Rossor, Martin N.; Fox, Nick C.; Warren, Jason D.; Spillantini, Maria Grazia; Morris, Huw R.; Rizzu, Patrizia; Heutink, Peter; Snowden, Julie S.; Rollinson, Sara; Richardson, Anna; Gerhard, Alexander; Bruni, Amalia C.; Maletta, Raffaele; Frangipane, Francesca; Cupidi, Chiara; Bernardi, Livia; Anfossi, Maria; Gallo, Maura; Conidi, Maria Elena; Smirne, Nicoletta; Rademakers, Rosa; Baker, Matt; Dickson, Dennis W.; Graff-Radford, Neill R.; Petersen, Ronald C.; Knopman, David; Josephs, Keith A.; Boeve, Bradley F.; Parisi, Joseph E.; Seeley, William W.; Karydas, Anna M.; Rosen, Howard; van Swieten, John C.; Dopper, Elise G. P.; Seelaar, Harro; Pijnenburg, Yolande A. L.; Scheltens, Philip; Logroscino, Giancarlo; Capozzo, Rosa; Novelli, Valeria; Puca, Annibale A.; Franceschi, Massimo; Postiglione, Alfredo; Milan, Graziella; Sorrentino, Paolo; Kristiansen, Mark; Chiang, Huei-Hsin; Graff, Caroline; Pasquier, Florence; Rollin, Adeline; Deramecourt, Vincent; Lebouvier, Thibaud; Kapogiannis, Dimitrios; Ferrucci, Luigi; Pickering-Brown, Stuart; Singleton, Andrew B. |
| Contributors: |
I. Broce; C.M. Karch; N. Wen; C.C. Fan; Y. Wang; C. Hong Tan; N. Kouri; O.A. Ro; G.U. Höglinger; U. Muller; J. Hardy; P. Momeni; C.P. He; W.P. Dillon; Z.A. Miller; L.W. Bonham; G.D. Rabinovici; H.J. Rosen; G.D. Schellenberg; A. Franke; T.H. Karlsen; J.H. Veldink; R. Ferrari; J.S. Yokoyama; B.L. Miller; O.A. Andreassen; A.M. Dale; R.S. Desikan; L.P. Sugrue; D.G. Hernandez; M.A. Nall; J.D. Rohrer; A. Ramasamy; J.B.J. Kwok; C. Dobson-Stone; W.S. Brook; P.R. Schofield; G.M. Halliday; J.R. Hodge; O. Piguet; L. Bartley; E. Thompson; E. Haan; I. Hernández; A. Ruiz; M. Boada; B. Borroni; A. Padovani; C. Cruchaga; N.J. Cairn; L. Benussi; G. Binetti; R. Ghidoni; G. Forloni; D. Albani; D. Galimberti; C. Fenoglio; M. Serpente; E. Scarpini; J. Clarimón; A. Lleó; R. Blesa; M. Landqvist Waldö; K. Nilsson; C. Nilsson; I.R.A. Mackenzie; G.R. Hsiung; D.M.A. Mann; J. Grafman; C.M. Morri; J. Attem; T.D. Griffith; I. G McKeith; A.J. Thoma; P. Pietrini; E.D. Huey; E.M. Wassermann; A. Baborie; E. Jaro; M.C. Tierney; P. Pastor; C. Razquin; S. Ortega-Cubero; E. Alonso; R. Perneczky; J. Diehl-Schmid; P. Alexopoulo; A. Kurz; I. Rainero; E. Rubino; L. Pinessi; E. Rogaeva; P. St George-Hyslop; G. Rossi; F. Tagliavini; G. Giaccone; J.B. Rowe; J.C.M. Schlachetzki; J. Uphill |
| Publisher Information: |
Public Library of Science |
| Publication Year: |
2018 |
| Collection: |
The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| Subject Terms: |
Progressive supranuclear palsy; amyotrophic-lateral-sclerosi; lobar degeneration; common variant; corticobasal degeneration; Parkinsons-disease; risk variant; identifies 7; loci; tau; Settore BIO/13 - Biologia Applicata; Settore MED/26 - Neurologia |
| 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/wos/WOS:000423818400008; volume:15; issue:1; firstpage:1; lastpage:20; numberofpages:20; journal:PLOS MEDICINE; https://hdl.handle.net/2434/635429 |
| DOI: |
10.1371/journal.pmed.1002487 |
| Availability: |
https://hdl.handle.net/2434/635429; https://doi.org/10.1371/journal.pmed.1002487 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.FF76BE79 |
| Database: |
BASE |