No Cover Image

Journal article 73 views 1 download

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Itziar de Rojas Orcid Logo, Sonia Moreno-Grau, Niccolo Tesi, Benjamin Grenier-Boley, Victor Andrade, Iris E. Jansen, Nancy L. Pedersen, Najada Stringa Orcid Logo, Anna Zettergren Orcid Logo, Isabel Hernández, Laura Montrreal, Carmen Antúnez, Anna Antonell, Rick M. Tankard Orcid Logo, Joshua C. Bis, Rebecca Sims Orcid Logo, Céline Bellenguez Orcid Logo, Inés Quintela, Antonio González-Perez, Miguel Calero Orcid Logo, Emilio Franco-Macías, Juan Macías, Rafael Blesa, Laura Cervera-Carles Orcid Logo, Manuel Menéndez-González Orcid Logo, Ana Frank-García, Jose Luís Royo, Fermin Moreno, Raquel Huerto Vilas, Miquel Baquero, Mónica Diez-Fairen Orcid Logo, Carmen Lage Orcid Logo, Sebastián García-Madrona, Pablo García-González Orcid Logo, Emilio Alarcón-Martín, Sergi Valero, Oscar Sotolongo-Grau, Abbe Ullgren, Adam C. Naj, Afina W. Lemstra, Alba Benaque, Alba Pérez-Cordón Orcid Logo, Alberto Benussi Orcid Logo, Alberto Rábano, Alessandro Padovani, Alessio Squassina Orcid Logo, Alexandre de Mendonça, Alfonso Arias Pastor, Almar A. L. Kok, Alun Meggy, Ana Belén Pastor Orcid Logo, Ana Espinosa, Anaïs Corma-Gómez, Angel Martín Montes Orcid Logo, Ángela Sanabria, Anita L. DeStefano, Anja Schneider, Annakaisa Haapasalo Orcid Logo, Anne Kinhult Ståhlbom, Anne Tybjærg-Hansen, Annette M. Hartmann, Annika Spottke, Arturo Corbatón-Anchuelo, Arvid Rongve Orcid Logo, Barbara Borroni, Beatrice Arosio, Benedetta Nacmias Orcid Logo, Børge G. Nordestgaard Orcid Logo, Brian W. Kunkle, Camille Charbonnier, Carla Abdelnour, Carlo Masullo, Carmen Martínez Rodríguez, Carmen Muñoz-Fernandez, Carole Dufouil, Caroline Graff, Catarina B. Ferreira, Caterina Chillotti, Chandra A. Reynolds Orcid Logo, Chiara Fenoglio, Christine Van Broeckhoven Orcid Logo, Christopher Clark Orcid Logo, Claudia Pisanu Orcid Logo, Claudia L. Satizabal Orcid Logo, Clive Holmes, Dolores Buiza-Rueda, Dag Aarsland Orcid Logo, Dan Rujescu, Daniel Alcolea Orcid Logo, Daniela Galimberti Orcid Logo, David Wallon Orcid Logo, Davide Seripa, Edna Grünblatt Orcid Logo, Efthimios Dardiotis, Emrah Düzel, Elio Scarpini, Elisa Conti, Elisa Rubino, Ellen Gelpi, Eloy Rodriguez-Rodriguez Orcid Logo, Emmanuelle Duron, Eric Boerwinkle, Evelyn Ferri, Fabrizio Tagliavini, Fahri Küçükali Orcid Logo, Florence Pasquier Orcid Logo, Florentino Sanchez-Garcia, Francesca Mangialasche, Frank Jessen, Gaël Nicolas Orcid Logo, Geir Selbæk Orcid Logo, Gemma Ortega, Geneviève Chêne, Georgios Hadjigeorgiou, Giacomina Rossi, Gianfranco Spalletta, Giorgio Giaccone, Giulia Grande, Giuliano Binetti, Goran Papenberg, Harald Hampel, Henri Bailly, Henrik Zetterberg Orcid Logo, Hilkka Soininen Orcid Logo, Ida K. Karlsson, Ignacio Alvarez Orcid Logo, Ildebrando Appollonio, Ina Giegling, Ingmar Skoog, Ingvild Saltvedt Orcid Logo, Innocenzo Rainero, Irene Rosas Allende, Jakub Hort, Janine Diehl-Schmid, Jasper Van Dongen Orcid Logo, Jean-Sebastien Vidal Orcid Logo, Jenni Lehtisalo, Jens Wiltfang, Jesper Qvist Thomassen, Johannes Kornhuber Orcid Logo, Jonathan L. Haines Orcid Logo, Jonathan Vogelgsang Orcid Logo, Juan A. Pineda Orcid Logo, Juan Fortea, Julius Popp, Jürgen Deckert, Katharina Buerger, Kevin Morgan Orcid Logo, Klaus Fließbach, Kristel Sleegers Orcid Logo, Laura Molina-Porcel, Lena Kilander, Leonie Weinhold, Lindsay A. Farrer Orcid Logo, Li-San Wang, Luca Kleineidam, Lucia Farotti, Lucilla Parnetti, Lucio Tremolizzo, Lucrezia Hausner, Luisa Benussi, Lutz Froelich, M. Arfan Ikram Orcid Logo, M. Candida Deniz-Naranjo, Magda Tsolaki Orcid Logo, Maitée Rosende-Roca, Malin Löwenmark, Marc Hulsman, Marco Spallazzi, Margaret A. Pericak-Vance Orcid Logo, Margaret Esiri, María Bernal Sánchez-Arjona, Maria Carolina Dalmasso, María Teresa Martínez-Larrad, Marina Arcaro, Markus M. Nöthen, Marta Fernández-Fuertes, Martin Dichgans Orcid Logo, Martin Ingelsson, Martin J. Herrmann, Martin Scherer, Martin Vyhnalek, Mary H. Kosmidis, Mary Yannakoulia, Matthias Schmid, Michael Ewers Orcid Logo, Michael T. Heneka, Michael Wagner Orcid Logo, Michela Scamosci, Miia Kivipelto, Mikko Hiltunen, Miren Zulaica, Montserrat Alegret, Myriam Fornage, Natalia Roberto, Natasja M. van Schoor, Nazib M. Seidu, Nerisa Banaj, Nicola J. Armstrong, Nikolaos Scarmeas, Norbert Scherbaum, Oliver Goldhardt, Oliver Hanon, Oliver Peters, Olivia Anna Skrobot, Olivier Quenez Orcid Logo, Ondrej Lerch, Paola Bossù Orcid Logo, Paolo Caffarra, Paolo Dionigi Rossi, Paraskevi Sakka, Per Hoffmann, Peter A. Holmans Orcid Logo, Peter Fischer, Peter Riederer, Qiong Yang Orcid Logo, Rachel Marshall, Rajesh N. Kalaria, Richard Mayeux, Rik Vandenberghe, Roberta Cecchetti, Roberta Ghidoni, Ruth Frikke-Schmidt, Sandro Sorbi, Sara Hägg Orcid Logo, Sebastiaan Engelborghs, Seppo Helisalmi, Sigrid Botne Sando, Silke Kern, Silvana Archetti, Silvia Boschi, Silvia Fostinelli, Silvia Gil, Silvia Mendoza, Simon Mead, Simona Ciccone, Srdjan Djurovic Orcid Logo, Stefanie Heilmann-Heimbach, Steffi Riedel-Heller, Teemu Kuulasmaa, Teodoro del Ser, Thibaud Lebouvier, Thomas Polak, Tiia Ngandu, Timo Grimmer, Valentina Bessi Orcid Logo, Valentina Escott-Price Orcid Logo, Vilmantas Giedraitis Orcid Logo, Vincent Deramecourt, Wolfgang Maier, Xueqiu Jian Orcid Logo, Yolande A. L. Pijnenburg, A. David Smith, Aldo Saenz, Alessandra Bizzarro, Alessandra Lauria, Alessandro Vacca, Alina Solomon, Anna Anastasiou, Anna Richardson, Anne Boland, Anne Koivisto, Antonio Daniele, Antonio Greco, Arnaoutoglou Marianthi, Bernadette McGuinness, Bertrand Fin, Camilla Ferrari, Carlo Custodero, Carlo Ferrarese, Carlos Ingino, Carlos Mangone, Carlos Reyes Toso, Carmen Martínez, Carolina Cuesta, Carolina Muchnik, Catharine Joachim, Cecilia Ortiz, Céline Besse, Charlotte Johansson, Chiara Paola Zoia, Christoph Laske, Costas Anastasiou, Dana Lis Palacio, Daniel G. Politis, Daniel Janowitz, David Craig, David M. Mann, David Neary, Deckert Jürgen, Delphine Daian, Diyana Belezhanska, Eduardo Kohler, Eduardo M. Castaño, Effrosyni Koutsouraki, Elena Chipi, Ellen De Roeck, Emanuele Costantini, Emma R. L. C. Vardy, Fabrizio Piras, Fausto Roveta, Federica Piras, Federico Ariel Prestia, Francesca Assogna, Francesca Salani, Gessica Sala, Giordano Lacidogna, Gisela Novack, Gordon Wilcock, Håkan Thonberg, Heike Kölsch, Heike Weber, Henning Boecker, Ignacio Etchepareborda, Irene Piaceri, Jaakko Tuomilehto, Jaana Lindström, Jan Laczo, Janet Johnston, Jean-François Deleuze, Jenny Harris, Jonathan M. Schott, Josef Priller, Juan Ignacio Bacha, Julie Snowden, Julieta Lisso, Kalina Yonkova Mihova, Latchezar Traykov, Laura Morelli, Luis Ignacio Brusco, Malik Rainer, Mari Takalo, Maria Bjerke, Maria Del Zompo, Maria Serpente, Mariana Sanchez Abalos Orcid Logo, Mario Rios, Markku Peltonen, Martin J. Herrman, Mary H. Kosmidis, Matias Kohler, Matias Rojo, Matthew Jones, Michela Orsini, Nancy Medel, Natividad Olivar, Nick C. Fox, Nicola Salvadori, Nigel M. Hooper, Pablo Galeano, Patricia Solis, Patrizia Bastiani, Patrizia Mecocci, Peter Passmore, Reinhard Heun, Riitta Antikainen, Robert Olaso, Robert Perneczky, Sandra Germani, Sara López-García, Seth Love, Shima Mehrabian, Silvia Bagnoli, Silvia Kochen, Simona Andreoni, Stefan Teipel, Stephen Todd, Stuart Pickering-Brown, Teemu Natunen, Thomas Tegos, Tiina Laatikainen, Timo Strandberg, Tuomo M. Polvikoski, Vaclav Matoska, Valentina Ciullo, Valeria Cores, Vincenzo Solfrizzi, Viviana Lisetti, Zulma Sevillano, C. Abdelnour, N. Aguilera, E. Alarcon, M. Alegret, A. Benaque, M. Boada, M. Buendia, P. Cañabate, A. Carracedo, A. Corbatón-Anchuelo, I. de Rojas, S. Diego, A. Espinosa, A. Gailhajenet, P. García-González, S. Gil, M. Guitart, A. González-Pérez, I. Hernández, M. Ibarria, A. Lafuente, J. Macias, O. Maroñas, E. Martín, M. T. Martínez, M. Marquié, A. Mauleón, L. Montrreal, S. Moreno-Grau, M. Moreno, A. Orellana, G. Ortega, A. Pancho, E. Pelejá, A. Pérez-Cordon, J. A. Pineda, S. Preckler, I. Quintela, L. M. Real, M. Rosende-Roca, A. Ruiz, M. E. Sáez, A. Sanabria, M. Serrano-Rios, O. Sotolongo-Grau, L. Tárraga, S. Valero, L. Vargas, A. D. Adarmes-Gómez, E. Alarcón-Martín, M. D. Alonso, I. Álvarez, V. Álvarez, G. Amer-Ferrer, M. Antequera, C. Antúnez, M. Baquero, M. Bernal, R. Blesa, M. Boada, D. Buiza-Rueda, M. J. Bullido, J. A. Burguera, M. Calero, F. Carrillo, M. Carrión-Claro, M. J. Casajeros, J. Clarimón, J. M. Cruz-Gamero, M. M. de Pancorbo, I. de Rojas, T. del Ser, M. Diez-Fairen, R. Escuela, L. Garrote-Espina, J. Fortea, E. Franco-Macías, A. Frank-García, J. M. García-Alberca, S. Garcia Madrona, G. Garcia-Ribas, P. Gómez-Garre, I. Hernández, S. Hevilla, S. Jesús, M. A. Labrador Espinosa, C. Lage, A. Legaz, A. Lleó, A. Lopez de Munain, S. López-García, D. Macias-García, S. Manzanares, M. Marín, J. Marín-Muñoz, T. Marín, M. Marquié, A. Martín Montes, B. Martínez, C. Martínez, V. Martínez, P. Martínez-Lage Álvarez, M. Medina, M. Mendioroz Iriarte, M. Menéndez-González, P. Mir, J. L. Molinuevo, P. Pastor, J. Pérez Tur, T. Periñán-Tocino, R. Pineda-Sanchez, G. Piñol-Ripoll, A. Rábano, D. Real de Asúa, S. Rodrigo, E. Rodríguez-Rodríguez, J. L. Royo, A. Ruiz, R. Sanchez del Valle Díaz, P. Sánchez-Juan, I. Sastre, S. Valero, M. P. Vicente, R. Vigo-Ortega, L. Vivancos, C. Macleod, C. McCracken, Carol Brayne, Catherine Bresner, Detelina Grozeva, Eftychia Bellou, Ewen W. Sommerville, F. Matthews, Ganna Leonenko, Georgina Menzies, Gill Windle, Janet Harwood, Judith Phillips, K. Bennett, Lauren Luckuck, Linda Clare, Robert Woods, Salha Saad, Vanessa Burholt, Iris E. Jansen, Arvid Rongve, Patrick Gavin Kehoe Orcid Logo, Guillermo Garcia-Ribas, Pascual Sánchez-Juan Orcid Logo, Pau Pastor Orcid Logo, Jordi Pérez-Tur Orcid Logo, Gerard Piñol-Ripoll, Adolfo Lopez de Munain Orcid Logo, Jose María García-Alberca Orcid Logo, María J. Bullido Orcid Logo, Victoria Álvarez, Alberto Lleó Orcid Logo, Luis M. Real Orcid Logo, Pablo Mir, Miguel Medina Orcid Logo, Philip Scheltens, Henne Holstege Orcid Logo, Marta Marquié, María Eugenia Sáez Orcid Logo, Ángel Carracedo, Philippe Amouyel Orcid Logo, Gerard D. Schellenberg, Julie Williams Orcid Logo, Sudha Seshadri Orcid Logo, Cornelia M. van Duijn Orcid Logo, Karen A. Mather Orcid Logo, Raquel Sánchez-Valle, Manuel Serrano-Ríos, Adelina Orellana, Lluís Tárraga, Kaj Blennow Orcid Logo, Martijn Huisman, Ole A. Andreassen Orcid Logo, Danielle Posthuma, Jordi Clarimón, Mercè Boada Orcid Logo, Wiesje M. van der Flier Orcid Logo, Alfredo Ramirez Orcid Logo, Jean-Charles Lambert Orcid Logo, Sven J. van der Lee Orcid Logo, Agustín Ruiz Orcid Logo, (EADB contributors), (The GR@ACE study group), (DEGESCO consortium), (IGAP (ADGC, CHARGE, EADI, GERAD)), (PGC-ALZ consortia), Vanessa Burholt Orcid Logo

Nature Communications, Volume: 12, Issue: 1

Swansea University Author: Vanessa Burholt Orcid Logo

  • Common variants in Alzhiemers disease and risk stratification by polygenic risk scores Nature Communications Jun 21 (Offprint).pdf

    PDF | Version of Record

    This article is licensed under a Creative Commons Attribution 4.0 International License

    Download (4.29MB)

Abstract

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all avai...

Full description

Published in: Nature Communications
ISSN: 2041-1723
Published: Springer Science and Business Media LLC 2021
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa60591
Tags: Add Tag
No Tags, Be the first to tag this record!
Abstract: Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.
College: College of Human and Health Sciences
Funders: The present work has been performed as part of the doctoral program of I. de Rojas at the Universitat de Barcelona (Barcelona, Spain) supported by national grant from the Instituto de Salud Carlos III FI20/00215. The Genome Research @ Fundació ACE project (GR@ACE) is supported by Grifols SA, Fundación bancaria “La Caixa”, Fundació ACE, and CIBERNED. A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, PI17/01474, PI19/01240 and PI19/01301. This work was supported by Stichting Alzheimer Nederland (WE09.2014-03), Stichting Diorapthe, horstingstuit foundation, Memorabel (ZonMW project number 733050814, 733050512) and Stichting VUmc Fonds. This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Program—Neurodegenerative Disease Research (JPND) and also funded by Inserm, Institut Pasteur de Lille, the Lille Métropole Communauté Urbaine, the French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Université de Lille 2 and the Lille University Hospital. GERAD was supported by the Medical Research Council (Grant n° 503480), Alzheimer’s Research UK (Grant n° 503176), the Wellcome Trust (Grant n° 082604/2/07/Z) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) grant n° 01GI0102, 01GI0711, 01GI0420. CHARGE was partly supported by the NIA/NHLBI grants AG049505, AG058589, HL105756 and AGES contract N01–AG–12100, the Icelandic Heart Association, and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants: U01 AG032984, U24 AG021886, U01 AG016976, and the Alzheimer’s Association grant ADGC–10–196728.
Issue: 1