Title : Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing Language : English Author, co-author : Kunkle, Brian W. [> >] Grenier-Boley, Benjamin [> >] Sims, Rebecca [> >] Bis, Joshua C. [> >] Damotte, Vincent [> >] Naj, Adam C. [> >] Boland, Anne [> >] Vronskaya, Maria [> >] van der Lee, Sven J. [> >] Amlie-Wolf, Alexandre [> >] Bellenguez, Céline [> >] Frizatti, Aura [> >] Chouraki, Vincent [> >] Martin, Eden R. [> >] Sleegers, Kristel [> >] Badarinarayan, Nandini [> >] Jakobsdottir, Johanna [> >] Hamilton-Nelson, Kara L. [> >] Moreno-Grau, Sonia [> >] Olaso, Robert [> >] Raybould, Rachel [> >] Chen, Yuning [> >] Kuzma, Amanda B. [> >] Hiltunen, Mikko [> >] Morgan, Taniesha [> >] Ahmad, Shahzad [> >] Vardarajan, Badri N. [> >] Epelbaum, Jacques [> >] Hoffmann, Per [> >] Boada, Merce [> >] Beecham, Gary W. [> >] Garnier, Jean-Guillaume [> >] Harold, Denise [> >] Fitzpatrick, Annette L. [> >] Valladares, Otto [> >] Moutet, Marie-Laure [> >] Gerrish, Amy [> >] Smith, Albert V. [> >] Qu, Liming [> >] Bacq, Delphine [> >] Denning, Nicola [> >] Jian, Xueqiu [> >] Zhao, Yi [> >] Zompo, Maria Del [> >] Fox, Nick C. [> >] Choi, Seung-Hoan [> >] Mateo, Ignacio [> >] Hughes, Joseph T. [> >] Adams, Hieab H. [> >] Malamon, John [> >] Sanchez-Garcia, Florentino [> >] Patel, Yogen [> >] Brody, Jennifer A. [> >] Dombroski, Beth A. [> >] Naranjo, Maria Candida Deniz [> >] Daniilidou, Makrina [> >] Eiriksdottir, Gudny [> >] Mukherjee, Shubhabrata [> >] Wallon, David [> >] Uphill, James [> >] Aspelund, Thor [> >] Cantwell, Laura B. [> >] Garzia, Fabienne [> >] Galimberti, Daniela [> >] Hofer, Edith [> >] Butkiewicz, Mariusz [> >] Fin, Bertrand [> >] Scarpini, Elio [> >] Sarnowski, Chloe [> >] Bush, Will S. [> >] Meslage, Stéphane [> >] Kornhuber, Johannes [> >] White, Charles C. [> >] Song, Yuenjoo [> >] Barber, Robert C. [> >] Engelborghs, Sebastiaan [> >] Sordon, Sabrina [> >] Voijnovic, Dina [> >] Adams, Perrie M. [> >] Vandenberghe, Rik [> >] Mayhaus, Manuel [> >] Cupples, L. Adrienne [> >] Albert, Marilyn S. [> >] Deyn, Peter P. De [> >] Gu, Wei [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >] Himali, Jayanadra J. [> >] Beekly, Duane [> >] Squassina, Alessio [> >] Hartmann, Annette M. [> >] Orellana, Adelina [> >] Blacker, Deborah [> >] Rodriguez-Rodriguez, Eloy [> >] Lovestone, Simon [> >] Garcia, Melissa E. [> >] Doody, Rachelle S. [> >] Munoz-Fernadez, Carmen [> >] Sussams, Rebecca [> >] Lin, Honghuang [> >] Fairchild, Thomas J. [> >] Benito, Yolanda A. [> >] Holmes, Clive [> >] Karamuji -\vComi, Hata [> >] Frosch, Matthew P. [> >] Thonberg, Hakan [> >] Maier, Wolfgang [> >] Roschupkin, Gena [> >] Ghetti, Bernardino [> >] Giedraitis, Vilmantas [> >] Kawalia, Amit [> >] Li, Shuo [> >] Huebinger, Ryan M. [> >] Kilander, Lena [> >] Moebus, Susanne [> >] Hernández, Isabel [> >] Kamboh, M. Ilyas [> >] Brundin, Rosemarie [> >] Turton, James [> >] Yang, Qiong [> >] Katz, Mindy J. [> >] Concari, Letizia [> >] Lord, Jenny [> >] Beiser, Alexa S. [> >] Keene, C. Dirk [> >] Helisalmi, Seppo [> >] Kloszewska, Iwona [> >] Kukull, Walter A. [> >] Koivisto, Anne Maria [> >] Lynch, Aoibhinn [> >] Tarraga, Lluís [> >] Larson, Eric B. [> >] Haapasalo, Annakaisa [> >] Lawlor, Brian [> >] Mosley, Thomas H. [> >] Lipton, Richard B. [> >] Solfrizzi, Vincenzo [> >] Gill, Michael [> >] Longstreth, W. T. [> >] Montine, Thomas J. [> >] Frisardi, Vincenza [> >] Diez-Fairen, Monica [> >] Rivadeneira, Fernando [> >] Petersen, Ronald C. [> >] Deramecourt, Vincent [> >] Alvarez, Ignacio [> >] Salani, Francesca [> >] Ciaramella, Antonio [> >] Boerwinkle, Eric [> >] Reiman, Eric M. [> >] Fievet, Nathalie [> >] Rotter, Jerome I. [> >] Reisch, Joan S. [> >] Hanon, Olivier [> >] Cupidi, Chiara [> >] Uitterlinden, A. G. Andre [> >] Royall, Donald R. [> >] Dufouil, Carole [> >] Maletta, Raffaele Giovanni [> >] de Rojas, Itziar [> >] Sano, Mary [> >] Brice, Alexis [> >] Cecchetti, Roberta [> >] George-Hyslop, Peter St [> >] Ritchie, Karen [> >] Tsolaki, Magda [> >] Tsuang, Debby W. [> >] Dubois, Bruno [> >] Craig, David [> >] Wu, Chuang-Kuo [> >] Soininen, Hilkka [> >] Avramidou, Despoina [> >] Albin, Roger L. [> >] Fratiglioni, Laura [> >] Germanou, Antonia [> >] Apostolova, Liana G. [> >] Keller, Lina [> >] Koutroumani, Maria [> >] Arnold, Steven E. [> >] Panza, Francesco [> >] Gkatzima, Olymbia [> >] Asthana, Sanjay [> >] Hannequin, Didier [> >] Whitehead, Patrice [> >] Atwood, Craig S. [> >] Caffarra, Paolo [> >] Hampel, Harald [> >] Quintela, Inés [> >] Carracedo, Ángel [> >] Lannfelt, Lars [> >] Rubinsztein, David C. [> >] Barnes, Lisa L. [> >] Pasquier, Florence [> >] Frölich, Lutz [> >] Barral, Sandra [> >] McGuinness, Bernadette [> >] Beach, Thomas G. [> >] Johnston, Janet A. [> >] Becker, James T. [> >] Passmore, Peter [> >] Bigio, Eileen H. [> >] Schott, Jonathan M. [> >] Bird, Thomas D. [> >] Warren, Jason D. [> >] Boeve, Bradley F. [> >] Lupton, Michelle K. [> >] Bowen, James D. [> >] Proitsi, Petra [> >] Boxer, Adam [> >] Powell, John F. [> >] Burke, James R. [> >] Kauwe, John S. K. [> >] Burns, Jeffrey M. [> >] Mancuso, Michelangelo [> >] Buxbaum, Joseph D. [> >] Bonuccelli, Ubaldo [> >] Cairns, Nigel J. [> >] McQuillin, Andrew [> >] Cao, Chuanhai [> >] Livingston, Gill [> >] Carlson, Chris S. [> >] Bass, Nicholas J. [> >] Carlsson, Cynthia M. [> >] Hardy, John [> >] Carney, Regina M. [> >] Bras, Jose [> >] Carrasquillo, Minerva M. [> >] Guerreiro, Rita [> >] Allen, Mariet [> >] Chui, Helena C. [> >] Fisher, Elizabeth [> >] Masullo, Carlo [> >] Crocco, Elizabeth A. [> >] DeCarli, Charles [> >] Bisceglio, Gina [> >] Dick, Malcolm [> >] Ma, Li [> >] Duara, Ranjan [> >] Graff-Radford, Neill R. [> >] Evans, Denis A. [> >] Hodges, Angela [> >] Faber, Kelley M. [> >] Scherer, Martin [> >] Fallon, Kenneth B. [> >] Riemenschneider, Matthias [> >] Fardo, David W. [> >] Heun, Reinhard [> >] Farlow, Martin R. [> >] Kölsch, Heike [> >] Ferris, Steven [> >] Leber, Markus [> >] Foroud, Tatiana M. [> >] Heuser, Isabella [> >] Galasko, Douglas R. [> >] Giegling, Ina [> >] Gearing, Marla [> >] Hüll, Michael [> >] Geschwind, Daniel H. [> >] Gilbert, John R. [> >] Morris, John [> >] Green, Robert C. [> >] Mayo, Kevin [> >] Growdon, John H. [> >] Feulner, Thomas [> >] Hamilton, Ronald L. [> >] Harrell, Lindy E. [> >] Drichel, Dmitriy [> >] Honig, Lawrence S. [> >] Cushion, Thomas D. [> >] Huentelman, Matthew J. [> >] Hollingworth, Paul [> >] Hulette, Christine M. [> >] Hyman, Bradley T. [> >] Marshall, Rachel [> >] Jarvik, Gail P. [> >] Meggy, Alun [> >] Abner, Erin [> >] Menzies, Georgina E. [> >] Jin, Lee-Way [> >] Leonenko, Ganna [> >] Real, Luis M. [> >] Jun, Gyungah R. [> >] Baldwin, Clinton T. [> >] Grozeva, Detelina [> >] Karydas, Anna [> >] Russo, Giancarlo [> >] Kaye, Jeffrey A. [> >] Kim, Ronald [> >] Jessen, Frank [> >] Kowall, Neil W. [> >] Vellas, Bruno [> >] Kramer, Joel H. [> >] Vardy, Emma [> >] LaFerla, Frank M. [> >] Jöckel, Karl-Heinz [> >] Lah, James J. [> >] Dichgans, Martin [> >] Leverenz, James B. [> >] Mann, David [> >] Levey, Allan I. [> >] Pickering-Brown, Stuart [> >] Lieberman, Andrew P. [> >] Klopp, Norman [> >] Lunetta, Kathryn L. [> >] Wichmann, H.-Erich [> >] Lyketsos, Constantine G. [> >] Morgan, Kevin [> >] Marson, Daniel C. [> >] Brown, Kristelle [> >] Martiniuk, Frank [> >] Medway, Christopher [> >] Mash, Deborah C. [> >] Nöthen, Markus M. [> >] Masliah, Eliezer [> >] Hooper, Nigel M. [> >] McCormick, Wayne C. [> >] Daniele, Antonio [> >] McCurry, Susan M. [> >] Bayer, Anthony [> >] McDavid, Andrew N. [> >] Gallacher, John [> >] McKee, Ann C. [> >] van den Bussche, Hendrik [> >] Mesulam, Marsel [> >] Brayne, Carol [> >] Miller, Bruce L. 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[> >] Broeckhoven, Christine Van [> >] O'Donovan, Michael C. [> >] DeStefano, Anita L. [> >] Jones, Lesley [> >] Haines, Jonathan L. [> >] Deleuze, Jean-Francois [> >] Owen, Michael J. [> >] Gudnason, Vilmundur [> >] Mayeux, Richard [> >] Escott-Price, Valentina [> >] Psaty, Bruce M. [> >] Ramirez, Alfredo [> >] Wang, Li-San [> >] Ruiz, Agustin [> >] van Duijn, Cornelia M. [> >] Holmans, Peter A. [> >] Seshadri, Sudha [> >] Williams, Julie [> >] Amouyel, Phillippe [> >] Schellenberg, Gerard D. [> >] Lambert, Jean-Charles [> >] Pericak-Vance, Margaret A. [> >] Publication date : 2019 Journal title : Nature Genetics Publisher : Nature Publishing Group Volume : 51 Issue/season : 3 Pages : 414 Peer reviewed : Yes (verified by ORBilu ) Audience : International ISSN : 1061-4036 e-ISSN : 1546-1718 City : New York Country : United Kingdom Keywords : [en] Alzheimer's disease ; Gene expression ; Genome wide association studiesAbstract : [en] Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and A$\beta$ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10−7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.Research centres : Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) Target : Researchers ; Professionals Permalink : http://hdl.handle.net/10993/38969 DOI : 10.1038/s41588-019-0358-2 Other URL : https://www.nature.com/articles/s41588-019-0358-2 
