Article (Scientific journals)
Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
Kunkle, Brian W.; Grenier-Boley, Benjamin; Sims, Rebecca et al.
2019In Nature Genetics, 51 (3), p. 414
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Keywords :
Alzheimer's disease; Gene expression; Genome wide association studies
Abstract :
[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 center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Disciplines :
Genetics & genetic processes
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.
Riedel-Heller, Steffi
Miller, Carol A.
Miller, Joshua W.
Al-Chalabi, Ammar
Morris, John C.
Shaw, Christopher E.
Myers, Amanda J.
Wiltfang, Jens
O'Bryant, Sid
Olichney, John M.
Alvarez, Victoria
Parisi, Joseph E.
Singleton, Andrew B.
Paulson, Henry L.
Collinge, John
Perry, William R.
Mead, Simon
Peskind, Elaine
Cribbs, David H.
Rossor, Martin
Pierce, Aimee
Ryan, Natalie S.
Poon, Wayne W.
Nacmias, Benedetta
Potter, Huntington
Sorbi, Sandro
Quinn, Joseph F.
Sacchinelli, Eleonora
Raj, Ashok
Spalletta, Gianfranco
Raskind, Murray
Caltagirone, Carlo
Bossù, Paola
Orfei, Maria Donata
Reisberg, Barry
Clarke, Robert
Reitz, Christiane
Smith, A. David
Ringman, John M.
Warden, Donald
Roberson, Erik D.
Wilcock, Gordon
Rogaeva, Ekaterina
Bruni, Amalia Cecilia
Rosen, Howard J.
Gallo, Maura
Rosenberg, Roger N.
Ben-Shlomo, Yoav
Sager, Mark A.
Mecocci, Patrizia
Saykin, Andrew J.
Pastor, Pau
Cuccaro, Michael L.
Vance, Jeffery M.
Schneider, Julie A.
Schneider, Lori S.
Slifer, Susan
Seeley, William W.
Smith, Amanda G.
Sonnen, Joshua A.
Spina, Salvatore
Stern, Robert A.
Swerdlow, Russell H.
Tang, Mitchell
Tanzi, Rudolph E.
Trojanowski, John Q.
Troncoso, Juan C.
Deerlin, Vivianna M. Van
Eldik, Linda J. Van
Vinters, Harry V.
Vonsattel, Jean Paul
Weintraub, Sandra
Welsh-Bohmer, Kathleen A.
Wilhelmsen, Kirk C.
Williamson, Jennifer
Wingo, Thomas S.
Woltjer, Randall L.
Wright, Clinton B.
Yu, Chang-En
Yu, Lei
Saba, Yasaman
Pilotto, Alberto
Bullido, Maria J.
Peters, Oliver
Crane, Paul K.
Bennett, David
Bosco, Paola
Coto, Eliecer
Boccardi, Virginia
Jager, Phil L. De
Lleo, Alberto
Warner, Nick
Lopez, Oscar L.
Ingelsson, Martin
Deloukas, Panagiotis
Cruchaga, Carlos
Graff, Caroline
Gwilliam, Rhian
Fornage, Myriam
Goate, Alison M.
Sanchez-Juan, Pascual
Kehoe, Patrick G.
Amin, Najaf
Ertekin-Taner, Nilifur
Berr, Claudine
Debette, Stéphanie
Love, Seth
Launer, Lenore J.
Younkin, Steven G.
Dartigues, Jean-Francois
Corcoran, Chris
Ikram, M. Arfan
Dickson, Dennis W.
Nicolas, Gael
Campion, Dominique
Tschanz, Joann
Schmidt, Helena
Hakonarson, Hakon
Clarimon, Jordi
Munger, Ron
Schmidt, Reinhold
Farrer, Lindsay A.
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.
More authors (458 more) Less
External co-authors :
yes
Language :
English
Title :
Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing
Publication date :
2019
Journal title :
Nature Genetics
ISSN :
1546-1718
Publisher :
Nature Publishing Group, New York, United Kingdom
Volume :
51
Issue :
3
Pages :
414
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 04 March 2019

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