Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by <i>HLA-DRB1*04</i> subtypes
Yann Le Guen(Institut du Cerveau), Guo Luo(Stanford University), Aditya Ambati(Stanford University), Vincent Damotte(Inserm), Iris E. Jansen(Amsterdam Neuroscience), Eric Yu(Montreal Neurological Institute and Hospital), Aude Nicolas(Inserm), Itziar de Rojas(Instituto de Salud Carlos III), Thiago Peixoto Leal(Cleveland Clinic Lerner College of Medicine), Akinori Miyashita(Niigata University), Céline Bellenguez(Inserm), Michelle Mulan Lian(Agency for Science, Technology and Research), Kayenat Parveen(University of Cologne), Takashi Morizono(National Center for Geriatrics and Gerontology), Hyeonseul Park(Chosun University), Benjamin Grenier‐Boley(Inserm), Tatsuhiko Naito(The University of Tokyo), Fahri Küçükali(University of Antwerp), Seth D. Talyansky(Stanford University), Selina Yogeshwar(Einstein Center for Neurosciences Berlin), Vicente Peris Sempere(Stanford University), Wataru Satake(The University of Tokyo), Victoria Álvarez(Hospital Universitario Central de Asturias), Beatrice Arosio(University of Milan), Michaël E. Belloy(Stanford University), Luisa Benussi(Centro San Giovanni di Dio Fatebenefratelli), Anne Boland(Commissariat à l'Énergie Atomique et aux Énergies Alternatives), Barbara Borroni(University of Brescia), María J. Bullido(Instituto de Salud Carlos III), Paolo Caffarra(University of Parma), Jordi Clarimón(Universitat Autònoma de Barcelona), Antonio Daniele(Università Cattolica del Sacro Cuore), D.H. Darling(Stanford University), Stéphanie Debette(Université de Bordeaux), Jean‐François Deleuze(Commissariat à l'Énergie Atomique et aux Énergies Alternatives), Martin Dichgans(German Center for Neurodegenerative Diseases), Carole Dufouil(Université de Bordeaux), Emmanuel During(Stanford University), Emrah Düzel(German Center for Neurodegenerative Diseases), Daniela Galimberti(University of Milan), Guillermo García‐Ribas(Instituto Ramón y Cajal de Investigación Sanitaria), José María García‐Alberca(Instituto de Salud Carlos III), Pablo García-González(Fundació ACE), Vilmantas Giedraitis(Uppsala University), Oliver Goldhardt(TUM Klinikum), Caroline Graff(Karolinska University Hospital), Edna Grünblatt(University of Zurich), Olivier Hanon(Université Paris Cité), Lucrezia Hausner(Heidelberg University), Stefanie Heilmann‐Heimbach(University of Bonn), Henne Holstege(Amsterdam Neuroscience), Jakub Hort(Charles University), Yoo Jin Jung(Stanford University), Jürgen Deckert(Universitätsklinikum Würzburg), Silke Kern(Sahlgrenska University Hospital), Teemu Kuulasmaa(University of Eastern Finland), Kun Ho Lee(Chosun University), Ling Lin(Stanford University), Carlo Masullo(Università Cattolica del Sacro Cuore), Patrizia Mecocci(University of Perugia), Shima Mehrabian(Medical University of Sofia), Alexandre de Mendonça(University of Lisbon), Merçé Boada(Instituto de Salud Carlos III), Pablo Mir(Instituto de Salud Carlos III), Susanne Moebus(University of Duisburg-Essen), Fermín Moreno(Instituto de Salud Carlos III), Benedetta Nacmias(Don Carlo Gnocchi Foundation), Gaël Nicolas(Inserm), Shumpei Niida(National Center for Geriatrics and Gerontology), Børge G. Nordestgaard(University of Copenhagen), Goran Papenberg(Stockholm University), Janne M. Papma(Erasmus MC), Lucilla Parnetti(University of Perugia), Florence Pasquier(Inserm), Pau Pástor(University Hospital Mútua de Terrassa), Oliver Peters(German Center for Neurodegenerative Diseases), Yolande A.L. Pijnenburg(Amsterdam Neuroscience), Gerard Piñol‐Ripoll(Hospital Universitari de Santa Maria), Julius Popp(University of Zurich), Laura Molina‐Porcel(Hospital Clínic de Barcelona), Raquel Puerta(Fundació ACE), Jordi Pérez‐Tur(Consejo Superior de Investigaciones Científicas), Innocenzo Rainero(University of Turin), Inez H.G.B. Ramakers(Maastricht University), Luís Miguel Real(Hospital Universitario de Valme), Steffi G. Riedel‐Heller(Leipzig University), Eloy Rodríguez‐Rodríguez(Universidad de Cantabria), Owen A. Ross(Jacksonville College), José Luís Royo(Universidad de Málaga), Dan Rujescu(Martin Luther University Halle-Wittenberg), Nikolaos Scarmeas(National and Kapodistrian University of Athens), Philip Scheltens(Amsterdam Neuroscience), Norbert Scherbaum(University of Duisburg-Essen), Anja Schneider(University Hospital Bonn), Davide Seripa, Ingmar Skoog(University of Gothenburg), Vincenzo Solfrizzi(University of Bari Aldo Moro), Gianfranco Spalletta(Baylor College of Medicine), Alessio Squassina(University of Cagliari), John C. van Swieten(Erasmus MC), Raquel Sánchez‐Valle(Universitat de Barcelona), Eng‐King Tan(National University of Singapore), Thomas Tegos(Aristotle University of Thessaloniki), Charlotte E. Teunissen(Amsterdam Neuroscience), Jesper Qvist Thomassen(Copenhagen University Hospital), Lucio Tremolizzo(University of Milano-Bicocca), Martin Vyhnálek(Charles University), Frans Verhey(Maastricht University), Margda Wærn(Sahlgrenska University Hospital), Jens Wiltfang(German Center for Neurodegenerative Diseases), Jing Zhang(Stanford University), EADB(Sahlgrenska University Hospital), GR@ACE study group(Sahlgrenska University Hospital), DemGene(Stanford University), EADI(Cardiff University), GERAD(Inserm), Henrik Zetterberg(University of Cologne), Kaj Blennow(Sahlgrenska University Hospital), Zihuai He(Oslo University Hospital), Julie Williams(Erasmus MC), Philippe Amouyel(Inserm), Frank Jessen(University of Cologne), Patrick G. Kehoe(University of Copenhagen), Ole A. Andreassen(Oslo University Hospital), Cornelia van Duin(Erasmus MC), Magda Tsolaki(Aristotle University of Thessaloniki), Pascual Sánchez‐Juan(Uppsala University), Ruth Frikke‐Schmidt(University of Copenhagen), Kristel Sleegers(University of Antwerp), Tatsushi Toda(University of Eastern Finland), Anna Zettergren(Chosun University), Martin Ingelsson(Uppsala University), Yukinori Okada(Cardiff University), Giacomina Rossi(Agency for Science, Technology and Research), Mikko Hiltunen(University of Eastern Finland), Jungsoo Gim(Chosun University), Kouichi Ozaki(University of Cologne), Rebecca Sims(Cleveland Clinic Lerner College of Medicine), Jia Nee Foo(Agency for Science, Technology and Research), Wiesje M. van der Flier(Montreal Neurological Institute and Hospital), Takeshi Ikeuchi(Inserm), Alfredo Ramı́rez(University of Cologne), Ignácio F. Mata(Cleveland Clinic Lerner College of Medicine), Agustı́n Ruiz(Instituto de Salud Carlos III), Ziv Gan‐Or(Montreal Neurological Institute and Hospital), Jean‐Charles Lambert(Inserm), Michael D. Greicius(Stanford University), Emmanuel Mignot(Stanford University), Céline Bellenguez(Inserm), Fahri Küçükali(University of Antwerp), Iris E. Jansen(Amsterdam Neuroscience), Víctor Andrade, Sonia Moreno–Grau, Najaf Amin, Benjamin Grenier‐Boley(Inserm), Rafael Campos-Martín, Peter Holmans, Anne Boland(Commissariat à l'Énergie Atomique et aux Énergies Alternatives), Luca Kleineidam, Vincent Damotte(Inserm), Sven J. van der Lee, Teemu Kuulasmaa(University of Eastern Finland), Itziar de Rojas(Instituto de Salud Carlos III), Amber Yaqub, Ivana Prokic, Marcos R. Costa, Julien Chapuis, Shahzad Ahmad, Vilmantas Giedraitis(Uppsala University), Dag Aarsland, Pablo García‐González(Fundació ACE), Carla Abdelnour, Emilio Alarcón‐Martín, Daniel Alcolea, Montserrat Alegret, Ignacio Álvarez, Victoria Álvarez(Hospital Universitario Central de Asturias), Nicola J. Armstrong, Tsolaki Anthoula, Ildebrando Appollonio, Marina Arcaro, Silvana Archetti, Alfonso Arias Pastor, Beatrice Arosio(University of Milan), Lavinia Athanasiu, Henri Bailly, Nerisa Banaj, Miquel Baquero, Ana Belén Pastor, Luisa Benussi(Centro San Giovanni di Dio Fatebenefratelli), Claudine Berr, Céline Besse, Valentina Bessi, Giuliano Binetti, Alessandra Bizarro, Rafael Blesa, Merçé Boada(Instituto de Salud Carlos III), Barbara Borroni(University of Brescia), Silvia Boschi, Paola Bossù, Geir Bråthen, Catherine Bresner, Henry Brodaty, Keeley J. Brookes, Luis Ignacio Brusco, Dolores Buiza‐Rueda, Katharina Bürger, Vanessa Burholt, Miguel Calero, Geneviève Chêne, Ãngel Carracedo, Roberta Cecchetti, Laura Cervera‐Carles, Camille Charbonnier, Caterina Chillotti, Simona Ciccone, Jurgen A.H.R. Claassen, Jordi Clarimón(Universitat Autònoma de Barcelona), Christopher Clark, Elisa Conti, Anaïs Corma‐Gómez, Emanuele Maria Costantini, Carlo Custodero, Delphine Daian, Carolina Dalmasso, Antonio Daniele(Università Cattolica del Sacro Cuore), Efthimios Dardiotis, Jean‐François Dartigues, Peter Paul De Deyn, Stéphanie Debette(Université de Bordeaux), Jürgen Deckert, Teodoro del Ser, Nicola Denning, Martin Dichgans(German Center for Neurodegenerative Diseases), Janine Diehl‐Schmid, Mónica Díez-Fairén, Paolo Rossi, Srdjan Djurovic, Emmanuelle Duron, Emrah Düzel(German Center for Neurodegenerative Diseases), Carole Dufouil(Université de Bordeaux), Valentina Escott-Price, Ana Espinosa, Michael Ewers, Marta Fernández‐Fuertes, Catarina B. Ferreira, Evelyn Ferri, Bertrand Fin, Peter Fischer, Tormod Fladby, Klaus Fließbach, Juan Fortea, Silvia Fostinelli, Nick C. Fox, Emlio Franco-Macías, María J. Bullido(Instituto de Salud Carlos III), Ana Frank, Lutz Froelich, Daniela Galimberti(University of Milan), José María García‐Alberca(Instituto de Salud Carlos III), Pablo García-González(Fundació ACE), Sebastián García‐Madrona, Guillermo García‐Ribas(Instituto Ramón y Cajal de Investigación Sanitaria), Roberta Ghidoni, Ina Giegling, Giaccone Giorgio, Oliver Goldhardt(TUM Klinikum), Antonio González-Pérez, Caroline Graff(Karolinska University Hospital), Giulia Grande, Emma Green, Timo Grimmer, Edna Grünblatt(University of Zurich), Tamar Guetta‐Baranes, Annakaisa Haapasalo, Georgios M. Hadjigeorgiou, Harald Hampel, Olivier Hanon(Université Paris Cité), John Hardy, Annette M. Hartmann, Lucrezia Hausner(Heidelberg University), Janet Harwood, Stefanie Heilmann‐Heimbach(University of Bonn), Seppo Helisalmi, Michael T. Heneka, Isabel Hernández, Martin J. Herrmann, Per Hoffmann, Clive Holmes, Henne Holstege(Amsterdam Neuroscience), Raquel Huerto Vilas, Marc Hulsman, Charlotte Johansson, Lena Kilander, Anne Kinhult Ståhlbom, Miia Kivipelto, Anne M. Koivisto, Johannes Kornhuber, Mary H. Kosmidis, Carmen Lage, Erika J. Laukka, Alessandra Lauria, Jenni Lehtisalo, Ondřej Lerch, Alberto Lleó, Adolfo Lopez de Munain, Malin Löwemark, Lauren Luckcuck, Juan Macı́as, Catherine Macleod, Wolfgang Maier, Francesca Mangialasche, Spallazzi Marco, Marta Marquié, Iain Marshall, Ángel Martín Montes, Carmen Martínez Rodríguez, Carlo Masullo(Università Cattolica del Sacro Cuore), Simon Mead, Patrizia Mecocci(University of Perugia), Miguel Medina, Alun Meggy, Shima Mehrabian(Medical University of Sofia), Silvia Mendoza, Manuel Menéndez‐González, Pablo Mir(Instituto de Salud Carlos III), Susanne Moebus(University of Duisburg-Essen), Merel O. Mol, Laura Molina‐Porcel, Laura Montrreal, Laura Morelli, Fermín Moreno(Instituto de Salud Carlos III), Kevin Morgan, Markus M. Möthen, Carolina Muchnik, Benedetta Nacmias(Don Carlo Gnocchi Foundation), Tiia Ngandu, Gaël Nicolas(Inserm), Børge G. Nordestgaard(University of Copenhagen), Robert Olaso, Adelina Orellana, Michela Orsini, Gemma Ortega, Alessandro Padovani, Paolo Caffarra, Goran Papenberg(Stockholm University), Lucilla Parnetti(University of Perugia), Pau Pástor(University Hospital Mútua de Terrassa), Alba Pérez‐Cordón, Jordi Pérez‐Tur(Consejo Superior de Investigaciones Científicas), Pierre Péricard, Oliver Peters(German Center for Neurodegenerative Diseases), Yolande A.L. Pijnenburg(Amsterdam Neuroscience), Juan A. Pineda, Gerard Piñol-Ripoll(Hospital Universitari de Santa Maria), Claudia Pisanu, Thomas Polak, Julius Popp(University of Zurich), Daniëlle Posthuma, Josef Priller, Raquel Puerta(Fundació ACE), Olivier Quenez, Inés Quintela, Jesper Qvist Thomassen(Copenhagen University Hospital), Alberto Rábano, Innocenzo Rainero(University of Turin), Inez Ramakers(Maastricht University), Luís Miguel Real(Hospital Universitario de Valme), Marcel Reinders, Steffi G. Riedel‐Heller(Leipzig University), Peter Riederer, Natalia Roberto, Eloy Rodríguez‐Rodríguez(Universidad de Cantabria), Arvid Rongve, Irene Rosas Allende, Maitée Rosende‐Roca, José Luís Royo(Universidad de Málaga), Elisa Rubino, Dan Rujescu(Martin Luther University Halle-Wittenberg), María Eugenia Sáez, Paraskevi Sakka, Ingvild Saltvedt, Ángela Sanabria, María Bernal Sánchez‐Arjona, Florentino Sánchez-García, Pascual Sánchez‐Juan, Raquel Sánchez‐Valle(Universitat de Barcelona), Sigrid Botne Sando, Michela Scamosci, Nikolaos Scarmeas(National and Kapodistrian University of Athens), Elio Scarpini, Philip Scheltens(Amsterdam Neuroscience), Norbert Scherbaum(University of Duisburg-Essen), Martin Scherer, Matthias Schmid, Anja Schneider(University Hospital Bonn), Jonathan M. Schott, Geir Selbæk, Davide Seripa, Alexey A Shadrin, Olivia Anna Skrobot, Hilkka Soininen, Vincenzo Solfrizzi(University of Bari Aldo Moro), Alina Solomon, Sandro Sorbi, Óscar Sotolongo‐Grau, Gianfranco Spalletta(Baylor College of Medicine), Annika Spottke, Alessio Squassina(University of Cagliari), Eystein Stordal, Juan Pablo Tartan, Lluís Tárraga, Niccoló Tesi, Anbupalam Thalamuthu, Thomas Tegos, Latchezar Traykov, Lucio Tremolizzo(University of Milano-Bicocca), Anne Tybjærg‐Hansen, André G. Uitterlinden, Abbe Ullgren, Ingun Ulstein, Sergi Valero, Aad van der Lugt, Jasper Van Dongen, Jeroen van Rooij, John C. van Swieten(Erasmus MC), Rik Vandenberghe, Frans Verhey(Maastricht University), Jean‐Sébastien Vidal, Jonathan Vogelgsang, Martin Vyhnálek(Charles University), Michael Wagner, David Wallon, Leonie Weinhold, Jens Wiltfang(German Center for Neurodegenerative Diseases), Gill Windle, Bob Woods, Mary Yannakoulia, Miren Zulaica, Jan Laczó, Václav Maťoška, María Serpente, Francesca Assogna, Fabrizio Piras, Federica Piras, Valentina Ciullo, Jacob Shofany, Carlo Ferrarese, Simona Andreoni, Gessica Sala, C Zoia, Maria Del Zompo, Alberto Benussi, Patrizia Bastiani, Mari Takalo, Teemu Natunen, Tiina Laatikainen, Jaakko Tuomilehto, Riitta Antikaínen, Timo Strandberg, Jaana Lindström, Markku Peltonen, Richard Abraham, Ammar Al-Chalabi, Nicholas Bass, Carol Brayne, Kristelle S. Brown, John Collinge, David W. Craig, Pangiotis Deloukas, Nick C. Fox, Amy Gerrish, Michael Gill, Rhian Gwilliam, John Hardy, Denise Harold, Paul Hollingworth, Jarret A. Johnston, Lesley Jones, Brian Lawlor, Gill Livingston, Simon Lovestone, Michelle K. Lupton, Aoibhinn Lynch, David Mann, Bernadette McGuinness, Andrew McQuillin, Michael O‘Donovan, Michael J. Owen, Peter Passmore, John Powell, Petra Proitsi, Martin Rossor, Christopher E. Shaw, A. David Smith, Hugh Gurling, Stephen Todd, Catherine J. Mummery, Nathalie Ryan, Giordano Lacidogna, Ad Adarmes-Gómez, Ana Mauleón, Ana Pancho, A. Gailhajenet, Asunción Lafuente, Daniel Macías‐García, Elvira Martín, Esther Pelejà, F Carrillo, Isabel Sastre Merlín, L. Garrote-Espina, Liliana Vargas, Mario Carrión‐Claro, María Esmeralda Arreola Marín, Ma Labrador, Mar Buendía, M. D. Alonso, Marina Guitart, Mariona Moreno, Marta Ibarria, Mt Periñán, Núria Aguilera, P Gómez-Garre, Pilar Cañabate, R Escuela, R. Pineda-Sanchez, R Vigo-Ortega, Silvia Jesús, Sílvia Preckler, Silvia Rodrigo‐Herrero, Susana Diego, Alessandro Vacca, Fausto Roveta, Nicola Salvadori, Elena Chipi, Henning Boecker, Christoph Laske, Robert Perneczky, Costas A. Anastasiou, Daniel Janowitz, Rainer Malik, Anna Anastasiou, Kayenat Parveen(University of Cologne), Carmen Lage, Sara López‐García, Anna Antonell, Kalina Mihova, Diyana Belezhanska, Heike Weber, Silvia Kochen, Patricia Solís, Nancy Medel, Julieta Lisso, Zulma Sevillano, Daniel Gustavo Politis, Valeria Cores, Carolina Cuesta, Cecilia Ortíz, Juan Ignacio Bacha, Mario Rios, Aldo Saenz, Mariana Sanchez Abalos, Eduardo Köhler, Dana Lis Palacio, Ignacio Etchepareborda, Matias Köhler, Gisela V. Novack, Federico Ariel Prestia, Pablo Galeano, Eduardo M. Castaño, Sandra Germani, Carlos Reyes Toso, Matias Rojo, Carlos A. Ingino, Carlos A. Mangone, Sebastiaan Engelborghs, Fabrizio Tagliavini, Sune Fallgaard Nielsen, Lucia Farotti, Chiara Fenoglio, Geert Jan Biessels, Seth Love, Patrick G. Kehoe(University of Bristol), Florence Pasquier(Inserm), Christine Van Broeckhoven, David C. Rubinsztein, Stefan Teipel, Nathalie Fiévet, Vincent Deramecourt, Charlotte Forsell, Håkan Thonberg, Maria Bjerke, Ellen De Roeck, Nicholas G. Martin, Natividad Olivar, Mohsen Ghanbari, Perminder S. Sachdev, Karen A. Mather, Frank Jessen(University of Cologne), M. Arfan Ikram, Alexandre de Mendonça(University of Lisbon), Jakub Hort(Charles University), Tsolaki Magda, Philippe Amouyel(Inserm), Julie Williams(Cardiff University), Ruth Frikke‐Schmidt(University of Copenhagen), Jordi Clarimón(Universitat Autònoma de Barcelona), Jean‐François Deleuze(Commissariat à l'Énergie Atomique et aux Énergies Alternatives), Giacomina Rossi(Fondazione IRCCS Istituto Neurologico Carlo Besta), Ole A. Andreassen(Oslo University Hospital), Martin Ingelsson(Uppsala University), Mikko Hiltunen(University of Eastern Finland), Kristel Sleegers(University of Antwerp), Cornelia M. van Duijn(Institut Pasteur de Lille), Rebecca Sims(Cardiff University), Wiesje M. van der Flier(Amsterdam Neuroscience), Agustı́n Ruiz(Instituto de Salud Carlos III), Alfredo Ramı́rez(University of Cologne), Jean‐Charles Lambert(Inserm), N. Aguilera, Estefanía Burgos Alarcón, Montserrat Alegret, Merçé Boada(Instituto de Salud Carlos III), Marie‐Annick Buendia, Amanda Cano, Pilar Cañabate, Ãngel Carracedo, Arturo Corbatón Anchuelo, Itziar de Rojas(Instituto de Salud Carlos III), S. Diego, Ana Espinosa, A. Gailhajenet, Pablo García‐González(Fundació ACE), M. Guitart, A González-Péerez, Marta Ibarria, A. Lafuente, Juan Macı́as, Olalla Maroñas, Elisabeth Martin, M.T.M. Martinez, M Marquié, Laura Montrreal, Sonia Moreno–Grau, M. Moreno, Raúl Núñez‐Llaves, C. Olivé, Adelina Orellana, Gemma Ortega, Ana Pancho, E. Pelejà, Alba Pérez‐Cordón, Juan A. Pineda, R Puerta(Fundació ACE), Sílvia Preckler, Inés Quintela, Luís Miguel Real(Hospital Universitario de Valme), Maitée Rosende‐Roca, Agustı́n Ruiz(Instituto de Salud Carlos III), ME Sáez, Ángela Sanabria, Manuel Serrano‐Ríos, Óscar Sotolongo‐Grau, L Táarraga, S Valero, Liliana Vargas, Ad Adarmes-Gómez, Emilio Alarcón‐Martín, MD Alonso, Ignacio Álvarez, Victoria Álvarez(Hospital Universitario Central de Asturias), G. Amer-Ferrer, M. Antequera, Carmen Antúnez, Miquel Baquero, M. Bernal, Rafael Blesa, Merçé Boada(Instituto de Salud Carlos III), Dolores Buiza‐Rueda, MJ Bullido(Instituto de Salud Carlos III), Burguera Ja, Miguel Calero, F Carrillo, Mario Carrión‐Claro, MJ Casajeros, Jordi Clarimón(Universitat Autònoma de Barcelona), JM Cruz-Gamero, Marian M. de Pancorbo, Itziar de Rojas(Instituto de Salud Carlos III), Teodoro del Ser, Mónica Díez-Fairén, R Escuela, L. Garrote-Espina, Juan Fortea, Emilio Franco, Ana Frank, JM García-Alberca(Instituto de Salud Carlos III), S. García Madrona, Guillermo García‐Ribas(Instituto Ramón y Cajal de Investigación Sanitaria), P Gómez-Garre, S. Hevilla, Silvia Jesús, MA Labrador Espinosa, Carmen Lage, A. Legaz, A Lleóo, A Lóopez de Munáin, Sara López‐García, Daniel Macías‐García, Salvadora Manzanares, María Esmeralda Arreola Marín, Juan Marín-Muñoz, T Marín, M Marquié, Ángel Martín Montes, B. Martínez, Carmen Martı́nez, Vicente Martı́nez, A Martínez-Lage Álvarez, Miguel Medina, M Mendioroz Iriarte, Manuel Menéndez‐González, Pablo Mir(Instituto de Salud Carlos III), Laura Montrreal, Adelina Orellana, Pau Pástor(University Hospital Mútua de Terrassa), J Péerez Tur, María Teresa Periñán, R. Pineda-Sanchez, G. Piñol Ripoll, A Ráabano, Diego Real de Asúa, S. Rodrigo, Eloy Rodríguez‐Rodríguez(Universidad de Cantabria), JL Royo(Universidad de Málaga), Agustı́n Ruiz(Instituto de Salud Carlos III), R. Sanchez del Valle Díaz, Pascual Sánchez‐Juan(Instituto de Salud Carlos III), Isabel Sastre, Óscar Sotolongo‐Grau, S Valero, MP Vicente, R Vigo-Ortega, L. Vivancos, Alexey A Shadrin, Shahram Bahrami, Arvid Rongve, Geir Bråthen, Ingunn Bosnes, Eystein Stordal, Lavinia Athanasiu, Per Selnes, Ingvild Saltvedt, Sigrid Botne Sando, Sverre Bergh, Ingun Ulstein, Srdjan Djurovic, Tormod Fladby, Dag Aarsland, Geir Selbæk, Ole A. Andreassen(Oslo University Hospital), Céline Bellenguez(Inserm), Benjamin Grenier‐Boley(Inserm), Jacques Epelbaum, David Wallon, Didier Hannequin, Florence Pasquier(Inserm), Claudine Berr, Jean‐François Dartigues, Dominique Campion, Christophe Tzourio, Vincent Dermecourt, Nathalie Fiévet, Olivier Hanon(Université Paris Cité), Carole Dufouil(Université de Bordeaux), Alexis Brice, Bruno Dubois, Karen Ritchie, Phillippe Amouyel(Inserm), Jean‐Charles Lambert(Inserm), Denise Harold, Paul Hollingworth, Rebecca Sims(Cardiff University), Amy Gerrish, Nicola Denning, Amy L. Williams, Charlene Thomas, Alun Meggy, Iain Marshall, Chloe Davies, Lauren Luckcuck, Will Nash, Kimberley Dowzell, Atahualpa Castillo-Morales, Mateus Bernardo-Harrington, Patrick G. Kehoe(University of Bristol), Per Hoffmann, Seth Love, James Turton, Jenny Lord, Kristelle Brown, Kevin Morgan, Emma Vardy, Elizabeth Fisher, Jason D. Warren, Jonathan M. Schott, Martin Rossor, Natalie S. Ryan, Nick C. Fox, Rita Guerreiro, Simon Mead, James Uphill, John Collinge, Michelle K. Lupton, Ammar Al-Chalabi, Christopher E. Shaw, Nick Bass, Richard Abraham, Reinhard Heun, Heike Kölsch, Britta Schürmann, Frank Jessen(University of Cologne), Wolfgang Maier, ndré Lacour, Christine Herold, Simon Lovestone, Bernadette McGuinness, David W. Craig, Janet Johnston, Michael Gill, Peter Passmore, Stephen Todd, John Powell, Petra Proitsi, Yogen Patel, Angela Hodges, Tim Becker, A. David Smith, Donald Warden, Gordon Wilcock, Robert Clarke, Aoibhinn Lynch, Brian Lawlor, Michael Gill, Andrew McQuillin, Gill Livingston, John Hardy, David C. Rubinsztein, Carol Brayne, Rhian Gwilliam, Panagiotis Deloukas, Yoav Ben‐Shlomo, David Mann, Nigel M. Hooper, Stuart Pickering‐Brown, Clive Holmes, Rebecca Sussams, Nick Warner, Anthony Bayer, Andrew Singleton, Annette M. Hartmann, Dan Rujescu(Martin Luther University Halle-Wittenberg), Ina Giegling, Harald Hampel, Martin Dichgans(German Center for Neurodegenerative Diseases), Isabella Heuser, Dmitriy Drichel, Norman Klopp, Markus M. Nöthen, Manuel Mayhaus, Matthias Riemenschneider, Sabrina Pinchler, Thomas Feulner, Wei Gu, Hendrik den Bussche, Martin Scherer, Jens Wiltfang(German Center for Neurodegenerative Diseases), Johannes Kornhuber, Michael Hüll, Lutz Frölich, H‐Erich Wichmann, Karl‐Heinz Jöckel, Susanne Moebus(University of Duisburg-Essen), Steffi G. Riedel‐Heller(Leipzig University), John Kauwe, John C. Morris, Kevin H. Mayo, Magda Tsolaki(Aristotle University of Thessaloniki), Michael O‘Donovan, Lesley Jones, Michael J. Owen, Valentina Escott-Price, Alfredo Ramı́rez(University of Cologne), Peter Holmans, Julie Williams(Cardiff University), Jia Nee Foo(Agency for Science, Technology and Research), Elaine Guo Yan Chew, Sun Ju Chung, Rong Peng, Yinxia Chao, Louis Tan, Moses Tandiono, Michelle Mulan Lian(Agency for Science, Technology and Research), Ebonne Ng, Kumar‐M. Prakash, Wing‐Lok Au, Wee-Yang Meah, Shi Qi Mok, Azlina Ahmad‐Annuar, Anne Chan, Ling Chen, Yongping Chen, Beom S. Jeon, Lulu Jiang, Jia Lun Lim, Juei‐Jueng Lin, Chun‐Feng Liu, Chengjie Mao, Vincent Mok, Zhong Pei, Huifang Shang, Changhe Shi, Kyuyoung Song, Ai Huey Tan, Yih‐Ru Wu, Yuming Xu, Renshi Xu, Yaping Yan, Jing Yang, Bao Rong Zhang, Woon‐Puay Koh, Shen‐Yang Lim, Chiea Chuen Khor, Jianjun Liu, Eng‐King Tan(National University of Singapore)
Cited by 48Open Access
Abstract
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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