Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

Brian W. Kunkle, Benjamin Grenier-Boley, Rebecca Sims, Joshua C. Bis, Vincent Damotte, Adam C. Naj, Anne Boland, Maria Vronskaya, Sven J. van der Lee, Alexandre Amlie-Wolf, Céline Bellenguez, Aura Frizatti, Vincent Chouraki, Eden R. Martin, Kristel Sleegers, Nandini Badarinarayan, Johanna Jakobsdottir, Kara L. Hamilton-Nelson, Sonia Moreno-Grau, Robert OlasoRachel Raybould, Yuning Chen, Amanda B. Kuzma, Mikko Hiltunen, Taniesha Morgan, Shahzad Ahmad, Badri N. Vardarajan, Jacques Epelbaum, Per Hoffmann, Merce Boada, Gary W. Beecham, Jean Guillaume Garnier, Denise Harold, Annette L. Fitzpatrick, Otto Valladares, Marie Laure Moutet, Amy Gerrish, Albert V. Smith, Liming Qu, Delphine Bacq, Nicola Denning, Xueqiu Jian, Yi Zhao, Maria Del Zompo, Nick C. Fox, Seung Hoan Choi, Ignacio Mateo, Joseph T. Hughes, Hieab H. Adams, John Malamon, Florentino Sanchez-Garcia, Yogen Patel, Jennifer A. Brody, Beth A. Dombroski, Maria Candida Deniz Naranjo, Makrina Daniilidou, Gudny Eiriksdottir, Shubhabrata Mukherjee, David Wallon, James Uphill, Thor Aspelund, Laura B. Cantwell, Fabienne Garzia, Daniela Galimberti, Edith Hofer, Mariusz Butkiewicz, Bertrand Fin, Elio Scarpini, Chloe Sarnowski, Will S. Bush, Stéphane Meslage, Johannes Kornhuber, Charles C. White, Yuenjoo Song, Robert C. Barber, Sebastiaan Engelborghs, Sabrina Sordon, Dina Voijnovic, Perrie M. Adams, Rik Vandenberghe, Manuel Mayhaus, L. Adrienne Cupples, Marilyn S. Albert, Peter P. De Deyn, Wei Gu, Jayanadra J. Himali, Duane Beekly, Alessio Squassina, Annette M. Hartmann, Adelina Orellana, Deborah Blacker, Eloy Rodriguez-Rodriguez, Simon Lovestone, Melissa E. Garcia, Rachelle S. Doody, Carmen Munoz-Fernadez, Rebecca Sussams, Honghuang Lin, Thomas J. Fairchild, Yolanda A. Benito, Clive Holmes, Hata Karamujić-Čomić, Matthew P. Frosch, Hakan Thonberg, Wolfgang Maier, Gena Roschupkin, Bernardino Ghetti, Vilmantas Giedraitis, Amit Kawalia, Shuo Li, Ryan M. Huebinger, Lena Kilander, Susanne Moebus, Isabel Hernández, M. Ilyas Kamboh, Rose Marie Brundin, James Turton, Qiong Yang, Mindy J. Katz, Letizia Concari, Jenny Lord, Alexa S. Beiser, C. Dirk Keene, Seppo Helisalmi, Iwona Kloszewska, Walter A. Kukull, Anne Maria Koivisto, Aoibhinn Lynch, Lluís Tarraga, Eric B. Larson, Annakaisa Haapasalo, Brian Lawlor, Thomas H. Mosley, Richard B. Lipton, Vincenzo Solfrizzi, Michael Gill, W. T. Longstreth, Thomas J. Montine, Vincenza Frisardi, Monica Diez-Fairen, Fernando Rivadeneira, Ronald C. Petersen, Vincent Deramecourt, Ignacio Alvarez, Francesca Salani, Antonio Ciaramella, Eric Boerwinkle, Eric M. Reiman, Nathalie Fievet, Jerome I. Rotter, Joan S. Reisch, Olivier Hanon, Chiara Cupidi, A. G. Andre Uitterlinden, Donald R. Royall, Carole Dufouil, Raffaele Giovanni Maletta, Itziar de Rojas, Mary Sano, Alexis Brice, Roberta Cecchetti, Peter St George-Hyslop, Karen Ritchie, Magda Tsolaki, Debby W. Tsuang, Bruno Dubois, David Craig, Chuang Kuo Wu, Hilkka Soininen, Despoina Avramidou, Roger L. Albin, Laura Fratiglioni, Antonia Germanou, Liana G. Apostolova, Lina Keller, Maria Koutroumani, Steven E. Arnold, Francesco Panza, Olymbia Gkatzima, Sanjay Asthana, Didier Hannequin, Patrice Whitehead, Craig S. Atwood, Paolo Caffarra, Harald Hampel, Inés Quintela, Ángel Carracedo, Lars Lannfelt, David C. Rubinsztein, Lisa L. Barnes, Florence Pasquier, Lutz Frölich, Sandra Barral, Bernadette McGuinness, Thomas G. Beach, Janet A. Johnston, James T. Becker, Peter Passmore, Eileen H. Bigio, Jonathan M. Schott, Thomas D. Bird, Jason D. Warren, Bradley F. Boeve, Michelle K. Lupton, James D. Bowen, Petra Proitsi, Adam Boxer, John F. Powell, James R. Burke, John S.K. Kauwe, Jeffrey M. Burns, Michelangelo Mancuso, Joseph D. Buxbaum, Ubaldo Bonuccelli, Nigel J. Cairns, Andrew McQuillin, Chuanhai Cao, Gill Livingston, Chris S. Carlson, Nicholas J. Bass, Cynthia M. Carlsson, John Hardy, Regina M. Carney, Jose Bras, Minerva M. Carrasquillo, Rita Guerreiro, Mariet Allen, Helena C. Chui, Elizabeth Fisher, Carlo Masullo, Elizabeth A. Crocco, Charles DeCarli, Gina Bisceglio, Malcolm Dick, Li Ma, Ranjan Duara, Neill R. Graff-Radford, Denis A. Evans, Angela Hodges, Kelley M. Faber, Martin Scherer, Kenneth B. Fallon, Matthias Riemenschneider, David W. Fardo, Reinhard Heun, Martin R. Farlow, Heike Kölsch, Steven Ferris, Markus Leber, Tatiana M. Foroud, Isabella Heuser, Douglas R. Galasko, Ina Giegling, Marla Gearing, Michael Hüll, Daniel H. Geschwind, John R. Gilbert, John C. Morris, Robert C. Green, Kevin Mayo, John H. Growdon, Thomas Feulner, Ronald L. Hamilton, Lindy E. Harrell, Dmitriy Drichel, Lawrence S. Honig, Thomas D. Cushion, Matthew J. Huentelman, Paul Hollingworth, Christine M. Hulette, Bradley T. Hyman, Rachel Marshall, Gail P. Jarvik, Alun Meggy, Erin Abner, Georgina E. Menzies, Lee Way Jin, Ganna Leonenko, Luis M. Real, Gyungah R. Jun, Clinton T. Baldwin, Detelina Grozeva, Anna Karydas, Giancarlo Russo, Jeffrey A. Kaye, Ronald Kim, Frank Jessen, Neil W. Kowall, Bruno Vellas, Joel H. Kramer, Emma Vardy, Frank M. LaFerla, Karl Heinz Jöckel, James J. Lah, Martin Dichgans, James B. Leverenz, David Mann, Allan I. Levey, Stuart Pickering-Brown, Andrew P. Lieberman, Norman Klopp, Kathryn L. Lunetta, H. Erich Wichmann, Constantine G. Lyketsos, Kevin Morgan, Daniel C. Marson, Kristelle Brown, Frank Martiniuk, Christopher Medway, Deborah C. Mash, Markus M. Nöthen, Eliezer Masliah, Nigel M. Hooper, Wayne C. McCormick, Antonio Daniele, Susan M. McCurry, Anthony Bayer, Andrew N. McDavid, John Gallacher, Ann C. McKee, Hendrik van den Bussche, Marsel Mesulam, Carol Brayne, Bruce L. Miller, Steffi Riedel-Heller, Carol A. Miller, Joshua W. Miller, Ammar Al-Chalabi, John C. Morris, Christopher E. Shaw, Amanda J. Myers, Jens Wiltfang, Sid O’Bryant, John M. Olichney, Victoria Alvarez, Joseph E. Parisi, Andrew B. Singleton, Henry L. Paulson, John Collinge, William R. Perry, Simon Mead, Elaine Peskind, David H. Cribbs, Martin Rossor, Aimee Pierce, Natalie S. Ryan, Wayne W. Poon, Benedetta Nacmias, Huntington Potter, Sandro Sorbi, Joseph G. Quinn, Eleonora Sacchinelli, Ashok Raj, Gianfranco Spalletta, Murray Raskind, Carlo Caltagirone, Paola Bossù, Maria Donata Orfei, Barry Reisberg, Robert Clarke, Christiane Reitz, A. David Smith, John M. Ringman, Donald Warden, Erik D. Roberson, Gordon Wilcock, Ekaterina Rogaeva, Amalia Cecilia Bruni, Howard J. Rosen, Maura Gallo, Roger N. Rosenberg, Yoav Ben-Shlomo, Mark A. Sager, Patrizia Mecocci, Andrew J. Saykin, Pau Pastor, Michael L. Cuccaro, Jeffery M. Vance, Julie A. Schneider, Lori S. Schneider, Susan Slifer, William W. Seeley, Amanda G. Smith, Joshua A. Sonnen, Salvatore Spina, Robert A. Stern, Russell H. Swerdlow, Mitchell Tang, Rudolph E. Tanzi, John Q. Trojanowski, Juan C. Troncoso, Vivianna M. Van Deerlin, Linda J. Van Eldik, Harry V. Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A. Welsh-Bohmer, Kirk C. Wilhelmsen, Jennifer Williamson, Thomas S. Wingo, Randall L. Woltjer, Clinton B. Wright, Chang En Yu, Lei Yu, Yasaman Saba, Alberto Pilotto, Maria J. Bullido, Oliver Peters, Paul K. Crane, David Bennett, Paola Bosco, Eliecer Coto, Virginia Boccardi, Phil L. De Jager, Alberto Lleo, Nick Warner, Oscar L. Lopez, Martin Ingelsson, Panagiotis Deloukas, Carlos Cruchaga, Caroline Graff, Rhian Gwilliam, Myriam Fornage, Alison M. Goate, Pascual Sanchez-Juan, Patrick G. Kehoe, Najaf Amin, Nilifur Ertekin-Taner, Claudine Berr, Stéphanie Debette, Seth Love, Lenore J. Launer, Steven G. Younkin, Jean Francois Dartigues, Chris Corcoran, M. Arfan Ikram, Dennis W. Dickson, Gael Nicolas, Dominique Campion, Jo Ann Tschanz, Helena Schmidt, Hakon Hakonarson, Jordi Clarimon, Ron Munger, Reinhold Schmidt, Lindsay A. Farrer, Christine Van Broeckhoven, Michael C. O’Donovan, Anita L. DeStefano, Lesley Jones, Jonathan L. Haines, Jean Francois Deleuze, Michael J. Owen, Vilmundur Gudnason, Richard Mayeux, Valentina Escott-Price, Bruce M. Psaty, Alfredo Ramirez, Li San Wang, Agustin Ruiz, Cornelia M. van Duijn, Peter A. Holmans, Sudha Seshadri, Julie Williams, Phillippe Amouyel, Gerard D. Schellenberg, Jean Charles Lambert, Margaret A. Pericak-Vance

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Abstract

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 Aβ 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.
Original languageEnglish
Pages (from-to)414-430
Number of pages17
JournalNature Genetics
Volume51
Issue number3
Early online date28 Feb 2019
DOIs
Publication statusPublished - 28 Feb 2019

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Meta-Analysis
Immunity
Alzheimer Disease
Lipids
Serum Amyloid A Protein
HLA Antigens
Dementia
Genome
Amyloidogenic Proteins
tau Proteins
Protein Precursors
Amyloid beta-Protein Precursor
Genome-Wide Association Study
Immune System Diseases
Proxy
Lipid Metabolism
Haplotypes
Carrier Proteins
Education
Genes

Cite this

Kunkle, B. W., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., ... Pericak-Vance, M. A. (2019). Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nature Genetics, 51(3), 414-430. https://doi.org/10.1038/s41588-019-0358-2
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 ; Del Zompo, Maria ; 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. ; De Deyn, Peter P. ; Gu, Wei ; 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 ; Karamujić-Čomić, 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, Rose Marie ; 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 ; Andre Uitterlinden, A. G. ; 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 C. ; 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 G. ; 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. ; Van Deerlin, Vivianna M. ; Van Eldik, Linda J. ; 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 ; De Jager, Phil L. ; 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, Jo Ann ; Schmidt, Helena ; Hakonarson, Hakon ; Clarimon, Jordi ; Munger, Ron ; Schmidt, Reinhold ; Farrer, Lindsay A. ; Van Broeckhoven, Christine ; C. O’Donovan, Michael ; 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. / Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. In: Nature Genetics. 2019 ; Vol. 51, No. 3. pp. 414-430.
@article{d9e9b5554b8a4262a4ba460b2dd62d13,
title = "Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing",
abstract = "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 Aβ 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.",
author = "Kunkle, {Brian W.} and Benjamin Grenier-Boley and Rebecca Sims and Bis, {Joshua C.} and Vincent Damotte and Naj, {Adam C.} and Anne Boland and Maria Vronskaya and {van der Lee}, {Sven J.} and Alexandre Amlie-Wolf and C{\'e}line Bellenguez and Aura Frizatti and Vincent Chouraki and Martin, {Eden R.} and Kristel Sleegers and Nandini Badarinarayan and Johanna Jakobsdottir and Hamilton-Nelson, {Kara L.} and Sonia Moreno-Grau and Robert Olaso and Rachel Raybould and Yuning Chen and Kuzma, {Amanda B.} and Mikko Hiltunen and Taniesha Morgan and Shahzad Ahmad and Vardarajan, {Badri N.} and Jacques Epelbaum and Per Hoffmann and Merce Boada and Beecham, {Gary W.} and Garnier, {Jean Guillaume} and Denise Harold and Fitzpatrick, {Annette L.} and Otto Valladares and Moutet, {Marie Laure} and Amy Gerrish and Smith, {Albert V.} and Liming Qu and Delphine Bacq and Nicola Denning and Xueqiu Jian and Yi Zhao and {Del Zompo}, Maria and Fox, {Nick C.} and Choi, {Seung Hoan} and Ignacio Mateo and Hughes, {Joseph T.} and Adams, {Hieab H.} and John Malamon and Florentino Sanchez-Garcia and Yogen Patel and Brody, {Jennifer A.} and Dombroski, {Beth A.} and Naranjo, {Maria Candida Deniz} and Makrina Daniilidou and Gudny Eiriksdottir and Shubhabrata Mukherjee and David Wallon and James Uphill and Thor Aspelund and Cantwell, {Laura B.} and Fabienne Garzia and Daniela Galimberti and Edith Hofer and Mariusz Butkiewicz and Bertrand Fin and Elio Scarpini and Chloe Sarnowski and Bush, {Will S.} and St{\'e}phane Meslage and Johannes Kornhuber and White, {Charles C.} and Yuenjoo Song and Barber, {Robert C.} and Sebastiaan Engelborghs and Sabrina Sordon and Dina Voijnovic and Adams, {Perrie M.} and Rik Vandenberghe and Manuel Mayhaus and Cupples, {L. Adrienne} and Albert, {Marilyn S.} and {De Deyn}, {Peter P.} and Wei Gu and Himali, {Jayanadra J.} and Duane Beekly and Alessio Squassina and Hartmann, {Annette M.} and Adelina Orellana and Deborah Blacker and Eloy Rodriguez-Rodriguez and Simon Lovestone and Garcia, {Melissa E.} and Doody, {Rachelle S.} and Carmen Munoz-Fernadez and Rebecca Sussams and Honghuang Lin and Fairchild, {Thomas J.} and Benito, {Yolanda A.} and Clive Holmes and Hata Karamujić-Čomić and Frosch, {Matthew P.} and Hakan Thonberg and Wolfgang Maier and Gena Roschupkin and Bernardino Ghetti and Vilmantas Giedraitis and Amit Kawalia and Shuo Li and Huebinger, {Ryan M.} and Lena Kilander and Susanne Moebus and Isabel Hern{\'a}ndez and Kamboh, {M. Ilyas} and Brundin, {Rose Marie} and James Turton and Qiong Yang and Katz, {Mindy J.} and Letizia Concari and Jenny Lord and Beiser, {Alexa S.} and Keene, {C. Dirk} and Seppo Helisalmi and Iwona Kloszewska and Kukull, {Walter A.} and Koivisto, {Anne Maria} and Aoibhinn Lynch and Llu{\'i}s Tarraga and Larson, {Eric B.} and Annakaisa Haapasalo and Brian Lawlor and Mosley, {Thomas H.} and Lipton, {Richard B.} and Vincenzo Solfrizzi and Michael Gill and Longstreth, {W. T.} and Montine, {Thomas J.} and Vincenza Frisardi and Monica Diez-Fairen and Fernando Rivadeneira and Petersen, {Ronald C.} and Vincent Deramecourt and Ignacio Alvarez and Francesca Salani and Antonio Ciaramella and Eric Boerwinkle and Reiman, {Eric M.} and Nathalie Fievet and Rotter, {Jerome I.} and Reisch, {Joan S.} and Olivier Hanon and Chiara Cupidi and {Andre Uitterlinden}, {A. G.} and Royall, {Donald R.} and Carole Dufouil and Maletta, {Raffaele Giovanni} and {de Rojas}, Itziar and Mary Sano and Alexis Brice and Roberta Cecchetti and George-Hyslop, {Peter St} and Karen Ritchie and Magda Tsolaki and Tsuang, {Debby W.} and Bruno Dubois and David Craig and Wu, {Chuang Kuo} and Hilkka Soininen and Despoina Avramidou and Albin, {Roger L.} and Laura Fratiglioni and Antonia Germanou and Apostolova, {Liana G.} and Lina Keller and Maria Koutroumani and Arnold, {Steven E.} and Francesco Panza and Olymbia Gkatzima and Sanjay Asthana and Didier Hannequin and Patrice Whitehead and Atwood, {Craig S.} and Paolo Caffarra and Harald Hampel and In{\'e}s Quintela and {\'A}ngel Carracedo and Lars Lannfelt and Rubinsztein, {David C.} and Barnes, {Lisa L.} and Florence Pasquier and Lutz Fr{\"o}lich and Sandra Barral and Bernadette McGuinness and Beach, {Thomas G.} and Johnston, {Janet A.} and Becker, {James T.} and Peter Passmore and Bigio, {Eileen H.} and Schott, {Jonathan M.} and Bird, {Thomas D.} and Warren, {Jason D.} and Boeve, {Bradley F.} and Lupton, {Michelle K.} and Bowen, {James D.} and Petra Proitsi and Adam Boxer and Powell, {John F.} and Burke, {James R.} and Kauwe, {John S.K.} and Burns, {Jeffrey M.} and Michelangelo Mancuso and Buxbaum, {Joseph D.} and Ubaldo Bonuccelli and Cairns, {Nigel J.} and Andrew McQuillin and Chuanhai Cao and Gill Livingston and Carlson, {Chris S.} and Bass, {Nicholas J.} and Carlsson, {Cynthia M.} and John Hardy and Carney, {Regina M.} and Jose Bras and Carrasquillo, {Minerva M.} and Rita Guerreiro and Mariet Allen and Chui, {Helena C.} and Elizabeth Fisher and Carlo Masullo and Crocco, {Elizabeth A.} and Charles DeCarli and Gina Bisceglio and Malcolm Dick and Li Ma and Ranjan Duara and Graff-Radford, {Neill R.} and Evans, {Denis A.} and Angela Hodges and Faber, {Kelley M.} and Martin Scherer and Fallon, {Kenneth B.} and Matthias Riemenschneider and Fardo, {David W.} and Reinhard Heun and Farlow, {Martin R.} and Heike K{\"o}lsch and Steven Ferris and Markus Leber and Foroud, {Tatiana M.} and Isabella Heuser and Galasko, {Douglas R.} and Ina Giegling and Marla Gearing and Michael H{\"u}ll and Geschwind, {Daniel H.} and Gilbert, {John R.} and Morris, {John C.} and Green, {Robert C.} and Kevin Mayo and Growdon, {John H.} and Thomas Feulner and Hamilton, {Ronald L.} and Harrell, {Lindy E.} and Dmitriy Drichel and Honig, {Lawrence S.} and Cushion, {Thomas D.} and Huentelman, {Matthew J.} and Paul Hollingworth and Hulette, {Christine M.} and Hyman, {Bradley T.} and Rachel Marshall and Jarvik, {Gail P.} and Alun Meggy and Erin Abner and Menzies, {Georgina E.} and Jin, {Lee Way} and Ganna Leonenko and Real, {Luis M.} and Jun, {Gyungah R.} and Baldwin, {Clinton T.} and Detelina Grozeva and Anna Karydas and Giancarlo Russo and Kaye, {Jeffrey A.} and Ronald Kim and Frank Jessen and Kowall, {Neil W.} and Bruno Vellas and Kramer, {Joel H.} and Emma Vardy and LaFerla, {Frank M.} and J{\"o}ckel, {Karl Heinz} and Lah, {James J.} and Martin Dichgans and Leverenz, {James B.} and David Mann and Levey, {Allan I.} and Stuart Pickering-Brown and Lieberman, {Andrew P.} and Norman Klopp and Lunetta, {Kathryn L.} and Wichmann, {H. Erich} and Lyketsos, {Constantine G.} and Kevin Morgan and Marson, {Daniel C.} and Kristelle Brown and Frank Martiniuk and Christopher Medway and Mash, {Deborah C.} and N{\"o}then, {Markus M.} and Eliezer Masliah and Hooper, {Nigel M.} and McCormick, {Wayne C.} and Antonio Daniele and McCurry, {Susan M.} and Anthony Bayer and McDavid, {Andrew N.} and John Gallacher and McKee, {Ann C.} and {van den Bussche}, Hendrik and Marsel Mesulam and Carol Brayne and Miller, {Bruce L.} and Steffi Riedel-Heller and Miller, {Carol A.} and Miller, {Joshua W.} and Ammar Al-Chalabi and Morris, {John C.} and Shaw, {Christopher E.} and Myers, {Amanda J.} and Jens Wiltfang and Sid O’Bryant and Olichney, {John M.} and Victoria Alvarez and Parisi, {Joseph E.} and Singleton, {Andrew B.} and Paulson, {Henry L.} and John Collinge and Perry, {William R.} and Simon Mead and Elaine Peskind and Cribbs, {David H.} and Martin Rossor and Aimee Pierce and Ryan, {Natalie S.} and Poon, {Wayne W.} and Benedetta Nacmias and Huntington Potter and Sandro Sorbi and Quinn, {Joseph G.} and Eleonora Sacchinelli and Ashok Raj and Gianfranco Spalletta and Murray Raskind and Carlo Caltagirone and Paola Boss{\`u} and Orfei, {Maria Donata} and Barry Reisberg and Robert Clarke and Christiane Reitz and Smith, {A. David} and Ringman, {John M.} and Donald Warden and Roberson, {Erik D.} and Gordon Wilcock and Ekaterina Rogaeva and Bruni, {Amalia Cecilia} and Rosen, {Howard J.} and Maura Gallo and Rosenberg, {Roger N.} and Yoav Ben-Shlomo and Sager, {Mark A.} and Patrizia Mecocci and Saykin, {Andrew J.} and Pau Pastor and Cuccaro, {Michael L.} and Vance, {Jeffery M.} and Schneider, {Julie A.} and Schneider, {Lori S.} and Susan Slifer and Seeley, {William W.} and Smith, {Amanda G.} and Sonnen, {Joshua A.} and Salvatore Spina and Stern, {Robert A.} and Swerdlow, {Russell H.} and Mitchell Tang and Tanzi, {Rudolph E.} and Trojanowski, {John Q.} and Troncoso, {Juan C.} and {Van Deerlin}, {Vivianna M.} and {Van Eldik}, {Linda J.} and Vinters, {Harry V.} and Vonsattel, {Jean Paul} and Sandra Weintraub and Welsh-Bohmer, {Kathleen A.} and Wilhelmsen, {Kirk C.} and Jennifer Williamson and Wingo, {Thomas S.} and Woltjer, {Randall L.} and Wright, {Clinton B.} and Yu, {Chang En} and Lei Yu and Yasaman Saba and Alberto Pilotto and Bullido, {Maria J.} and Oliver Peters and Crane, {Paul K.} and David Bennett and Paola Bosco and Eliecer Coto and Virginia Boccardi and {De Jager}, {Phil L.} and Alberto Lleo and Nick Warner and Lopez, {Oscar L.} and Martin Ingelsson and Panagiotis Deloukas and Carlos Cruchaga and Caroline Graff and Rhian Gwilliam and Myriam Fornage and Goate, {Alison M.} and Pascual Sanchez-Juan and Kehoe, {Patrick G.} and Najaf Amin and Nilifur Ertekin-Taner and Claudine Berr and St{\'e}phanie Debette and Seth Love and Launer, {Lenore J.} and Younkin, {Steven G.} and Dartigues, {Jean Francois} and Chris Corcoran and Ikram, {M. Arfan} and Dickson, {Dennis W.} and Gael Nicolas and Dominique Campion and Tschanz, {Jo Ann} and Helena Schmidt and Hakon Hakonarson and Jordi Clarimon and Ron Munger and Reinhold Schmidt and Farrer, {Lindsay A.} and {Van Broeckhoven}, Christine and {C. O’Donovan}, Michael and DeStefano, {Anita L.} and Lesley Jones and Haines, {Jonathan L.} and Deleuze, {Jean Francois} and Owen, {Michael J.} and Vilmundur Gudnason and Richard Mayeux and Valentina Escott-Price and Psaty, {Bruce M.} and Alfredo Ramirez and Wang, {Li San} and Agustin Ruiz and {van Duijn}, {Cornelia M.} and Holmans, {Peter A.} and Sudha Seshadri and Julie Williams and Phillippe Amouyel and Schellenberg, {Gerard D.} and Lambert, {Jean Charles} and Pericak-Vance, {Margaret A.}",
year = "2019",
month = "2",
day = "28",
doi = "10.1038/s41588-019-0358-2",
language = "English",
volume = "51",
pages = "414--430",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",

}

Kunkle, BW, Grenier-Boley, B, Sims, R, Bis, JC, Damotte, V, Naj, AC, Boland, A, Vronskaya, M, van der Lee, SJ, Amlie-Wolf, A, Bellenguez, C, Frizatti, A, Chouraki, V, Martin, ER, Sleegers, K, Badarinarayan, N, Jakobsdottir, J, Hamilton-Nelson, KL, Moreno-Grau, S, Olaso, R, Raybould, R, Chen, Y, Kuzma, AB, Hiltunen, M, Morgan, T, Ahmad, S, Vardarajan, BN, Epelbaum, J, Hoffmann, P, Boada, M, Beecham, GW, Garnier, JG, Harold, D, Fitzpatrick, AL, Valladares, O, Moutet, ML, Gerrish, A, Smith, AV, Qu, L, Bacq, D, Denning, N, Jian, X, Zhao, Y, Del Zompo, M, Fox, NC, Choi, SH, Mateo, I, Hughes, JT, Adams, HH, Malamon, J, Sanchez-Garcia, F, Patel, Y, Brody, JA, Dombroski, BA, Naranjo, MCD, Daniilidou, M, Eiriksdottir, G, Mukherjee, S, Wallon, D, Uphill, J, Aspelund, T, Cantwell, LB, Garzia, F, Galimberti, D, Hofer, E, Butkiewicz, M, Fin, B, Scarpini, E, Sarnowski, C, Bush, WS, Meslage, S, Kornhuber, J, White, CC, Song, Y, Barber, RC, Engelborghs, S, Sordon, S, Voijnovic, D, Adams, PM, Vandenberghe, R, Mayhaus, M, Cupples, LA, Albert, MS, De Deyn, PP, Gu, W, Himali, JJ, Beekly, D, Squassina, A, Hartmann, AM, Orellana, A, Blacker, D, Rodriguez-Rodriguez, E, Lovestone, S, Garcia, ME, Doody, RS, Munoz-Fernadez, C, Sussams, R, Lin, H, Fairchild, TJ, Benito, YA, Holmes, C, Karamujić-Čomić, H, Frosch, MP, Thonberg, H, Maier, W, Roschupkin, G, Ghetti, B, Giedraitis, V, Kawalia, A, Li, S, Huebinger, RM, Kilander, L, Moebus, S, Hernández, I, Kamboh, MI, Brundin, RM, Turton, J, Yang, Q, Katz, MJ, Concari, L, Lord, J, Beiser, AS, Keene, CD, Helisalmi, S, Kloszewska, I, Kukull, WA, Koivisto, AM, Lynch, A, Tarraga, L, Larson, EB, Haapasalo, A, Lawlor, B, Mosley, TH, Lipton, RB, Solfrizzi, V, Gill, M, Longstreth, WT, Montine, TJ, Frisardi, V, Diez-Fairen, M, Rivadeneira, F, Petersen, RC, Deramecourt, V, Alvarez, I, Salani, F, Ciaramella, A, Boerwinkle, E, Reiman, EM, Fievet, N, Rotter, JI, Reisch, JS, Hanon, O, Cupidi, C, Andre Uitterlinden, AG, Royall, DR, Dufouil, C, Maletta, RG, de Rojas, I, Sano, M, Brice, A, Cecchetti, R, George-Hyslop, PS, Ritchie, K, Tsolaki, M, Tsuang, DW, Dubois, B, Craig, D, Wu, CK, Soininen, H, Avramidou, D, Albin, RL, Fratiglioni, L, Germanou, A, Apostolova, LG, Keller, L, Koutroumani, M, Arnold, SE, Panza, F, Gkatzima, O, Asthana, S, Hannequin, D, Whitehead, P, Atwood, CS, Caffarra, P, Hampel, H, Quintela, I, Carracedo, Á, Lannfelt, L, Rubinsztein, DC, Barnes, LL, Pasquier, F, Frölich, L, Barral, S, McGuinness, B, Beach, TG, Johnston, JA, Becker, JT, Passmore, P, Bigio, EH, Schott, JM, Bird, TD, Warren, JD, Boeve, BF, Lupton, MK, Bowen, JD, Proitsi, P, Boxer, A, Powell, JF, Burke, JR, Kauwe, JSK, Burns, JM, Mancuso, M, Buxbaum, JD, Bonuccelli, U, Cairns, NJ, McQuillin, A, Cao, C, Livingston, G, Carlson, CS, Bass, NJ, Carlsson, CM, Hardy, J, Carney, RM, Bras, J, Carrasquillo, MM, Guerreiro, R, Allen, M, Chui, HC, Fisher, E, Masullo, C, Crocco, EA, DeCarli, C, Bisceglio, G, Dick, M, Ma, L, Duara, R, Graff-Radford, NR, Evans, DA, Hodges, A, Faber, KM, Scherer, M, Fallon, KB, Riemenschneider, M, Fardo, DW, Heun, R, Farlow, MR, Kölsch, H, Ferris, S, Leber, M, Foroud, TM, Heuser, I, Galasko, DR, Giegling, I, Gearing, M, Hüll, M, Geschwind, DH, Gilbert, JR, Morris, JC, Green, RC, Mayo, K, Growdon, JH, Feulner, T, Hamilton, RL, Harrell, LE, Drichel, D, Honig, LS, Cushion, TD, Huentelman, MJ, Hollingworth, P, Hulette, CM, Hyman, BT, Marshall, R, Jarvik, GP, Meggy, A, Abner, E, Menzies, GE, Jin, LW, Leonenko, G, Real, LM, Jun, GR, Baldwin, CT, Grozeva, D, Karydas, A, Russo, G, Kaye, JA, Kim, R, Jessen, F, Kowall, NW, Vellas, B, Kramer, JH, Vardy, E, LaFerla, FM, Jöckel, KH, Lah, JJ, Dichgans, M, Leverenz, JB, Mann, D, Levey, AI, Pickering-Brown, S, Lieberman, AP, Klopp, N, Lunetta, KL, Wichmann, HE, Lyketsos, CG, Morgan, K, Marson, DC, Brown, K, Martiniuk, F, Medway, C, Mash, DC, Nöthen, MM, Masliah, E, Hooper, NM, McCormick, WC, Daniele, A, McCurry, SM, Bayer, A, McDavid, AN, Gallacher, J, McKee, AC, van den Bussche, H, Mesulam, M, Brayne, C, Miller, BL, Riedel-Heller, S, Miller, CA, Miller, JW, Al-Chalabi, A, Morris, JC, Shaw, CE, Myers, AJ, Wiltfang, J, O’Bryant, S, Olichney, JM, Alvarez, V, Parisi, JE, Singleton, AB, Paulson, HL, Collinge, J, Perry, WR, Mead, S, Peskind, E, Cribbs, DH, Rossor, M, Pierce, A, Ryan, NS, Poon, WW, Nacmias, B, Potter, H, Sorbi, S, Quinn, JG, Sacchinelli, E, Raj, A, Spalletta, G, Raskind, M, Caltagirone, C, Bossù, P, Orfei, MD, Reisberg, B, Clarke, R, Reitz, C, Smith, AD, Ringman, JM, Warden, D, Roberson, ED, Wilcock, G, Rogaeva, E, Bruni, AC, Rosen, HJ, Gallo, M, Rosenberg, RN, Ben-Shlomo, Y, Sager, MA, Mecocci, P, Saykin, AJ, Pastor, P, Cuccaro, ML, Vance, JM, Schneider, JA, Schneider, LS, Slifer, S, Seeley, WW, Smith, AG, Sonnen, JA, Spina, S, Stern, RA, Swerdlow, RH, Tang, M, Tanzi, RE, Trojanowski, JQ, Troncoso, JC, Van Deerlin, VM, Van Eldik, LJ, Vinters, HV, Vonsattel, JP, Weintraub, S, Welsh-Bohmer, KA, Wilhelmsen, KC, Williamson, J, Wingo, TS, Woltjer, RL, Wright, CB, Yu, CE, Yu, L, Saba, Y, Pilotto, A, Bullido, MJ, Peters, O, Crane, PK, Bennett, D, Bosco, P, Coto, E, Boccardi, V, De Jager, PL, Lleo, A, Warner, N, Lopez, OL, Ingelsson, M, Deloukas, P, Cruchaga, C, Graff, C, Gwilliam, R, Fornage, M, Goate, AM, Sanchez-Juan, P, Kehoe, PG, Amin, N, Ertekin-Taner, N, Berr, C, Debette, S, Love, S, Launer, LJ, Younkin, SG, Dartigues, JF, Corcoran, C, Ikram, MA, Dickson, DW, Nicolas, G, Campion, D, Tschanz, JA, Schmidt, H, Hakonarson, H, Clarimon, J, Munger, R, Schmidt, R, Farrer, LA, Van Broeckhoven, C, C. O’Donovan, M, DeStefano, AL, Jones, L, Haines, JL, Deleuze, JF, Owen, MJ, Gudnason, V, Mayeux, R, Escott-Price, V, Psaty, BM, Ramirez, A, Wang, LS, Ruiz, A, van Duijn, CM, Holmans, PA, Seshadri, S, Williams, J, Amouyel, P, Schellenberg, GD, Lambert, JC & Pericak-Vance, MA 2019, 'Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing', Nature Genetics, vol. 51, no. 3, pp. 414-430. https://doi.org/10.1038/s41588-019-0358-2

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; 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; Del Zompo, Maria; 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.; De Deyn, Peter P.; Gu, Wei; 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; Karamujić-Čomić, 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, Rose Marie; 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; Andre Uitterlinden, A. G.; 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 C.; 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 G.; 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.; Van Deerlin, Vivianna M.; Van Eldik, Linda J.; 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; De Jager, Phil L.; 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, Jo Ann; Schmidt, Helena; Hakonarson, Hakon; Clarimon, Jordi; Munger, Ron; Schmidt, Reinhold; Farrer, Lindsay A.; Van Broeckhoven, Christine; C. O’Donovan, Michael; 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.

In: Nature Genetics, Vol. 51, No. 3, 28.02.2019, p. 414-430.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing

AU - Kunkle, Brian W.

AU - Grenier-Boley, Benjamin

AU - Sims, Rebecca

AU - Bis, Joshua C.

AU - Damotte, Vincent

AU - Naj, Adam C.

AU - Boland, Anne

AU - Vronskaya, Maria

AU - van der Lee, Sven J.

AU - Amlie-Wolf, Alexandre

AU - Bellenguez, Céline

AU - Frizatti, Aura

AU - Chouraki, Vincent

AU - Martin, Eden R.

AU - Sleegers, Kristel

AU - Badarinarayan, Nandini

AU - Jakobsdottir, Johanna

AU - Hamilton-Nelson, Kara L.

AU - Moreno-Grau, Sonia

AU - Olaso, Robert

AU - Raybould, Rachel

AU - Chen, Yuning

AU - Kuzma, Amanda B.

AU - Hiltunen, Mikko

AU - Morgan, Taniesha

AU - Ahmad, Shahzad

AU - Vardarajan, Badri N.

AU - Epelbaum, Jacques

AU - Hoffmann, Per

AU - Boada, Merce

AU - Beecham, Gary W.

AU - Garnier, Jean Guillaume

AU - Harold, Denise

AU - Fitzpatrick, Annette L.

AU - Valladares, Otto

AU - Moutet, Marie Laure

AU - Gerrish, Amy

AU - Smith, Albert V.

AU - Qu, Liming

AU - Bacq, Delphine

AU - Denning, Nicola

AU - Jian, Xueqiu

AU - Zhao, Yi

AU - Del Zompo, Maria

AU - Fox, Nick C.

AU - Choi, Seung Hoan

AU - Mateo, Ignacio

AU - Hughes, Joseph T.

AU - Adams, Hieab H.

AU - Malamon, John

AU - Sanchez-Garcia, Florentino

AU - Patel, Yogen

AU - Brody, Jennifer A.

AU - Dombroski, Beth A.

AU - Naranjo, Maria Candida Deniz

AU - Daniilidou, Makrina

AU - Eiriksdottir, Gudny

AU - Mukherjee, Shubhabrata

AU - Wallon, David

AU - Uphill, James

AU - Aspelund, Thor

AU - Cantwell, Laura B.

AU - Garzia, Fabienne

AU - Galimberti, Daniela

AU - Hofer, Edith

AU - Butkiewicz, Mariusz

AU - Fin, Bertrand

AU - Scarpini, Elio

AU - Sarnowski, Chloe

AU - Bush, Will S.

AU - Meslage, Stéphane

AU - Kornhuber, Johannes

AU - White, Charles C.

AU - Song, Yuenjoo

AU - Barber, Robert C.

AU - Engelborghs, Sebastiaan

AU - Sordon, Sabrina

AU - Voijnovic, Dina

AU - Adams, Perrie M.

AU - Vandenberghe, Rik

AU - Mayhaus, Manuel

AU - Cupples, L. Adrienne

AU - Albert, Marilyn S.

AU - De Deyn, Peter P.

AU - Gu, Wei

AU - Himali, Jayanadra J.

AU - Beekly, Duane

AU - Squassina, Alessio

AU - Hartmann, Annette M.

AU - Orellana, Adelina

AU - Blacker, Deborah

AU - Rodriguez-Rodriguez, Eloy

AU - Lovestone, Simon

AU - Garcia, Melissa E.

AU - Doody, Rachelle S.

AU - Munoz-Fernadez, Carmen

AU - Sussams, Rebecca

AU - Lin, Honghuang

AU - Fairchild, Thomas J.

AU - Benito, Yolanda A.

AU - Holmes, Clive

AU - Karamujić-Čomić, Hata

AU - Frosch, Matthew P.

AU - Thonberg, Hakan

AU - Maier, Wolfgang

AU - Roschupkin, Gena

AU - Ghetti, Bernardino

AU - Giedraitis, Vilmantas

AU - Kawalia, Amit

AU - Li, Shuo

AU - Huebinger, Ryan M.

AU - Kilander, Lena

AU - Moebus, Susanne

AU - Hernández, Isabel

AU - Kamboh, M. Ilyas

AU - Brundin, Rose Marie

AU - Turton, James

AU - Yang, Qiong

AU - Katz, Mindy J.

AU - Concari, Letizia

AU - Lord, Jenny

AU - Beiser, Alexa S.

AU - Keene, C. Dirk

AU - Helisalmi, Seppo

AU - Kloszewska, Iwona

AU - Kukull, Walter A.

AU - Koivisto, Anne Maria

AU - Lynch, Aoibhinn

AU - Tarraga, Lluís

AU - Larson, Eric B.

AU - Haapasalo, Annakaisa

AU - Lawlor, Brian

AU - Mosley, Thomas H.

AU - Lipton, Richard B.

AU - Solfrizzi, Vincenzo

AU - Gill, Michael

AU - Longstreth, W. T.

AU - Montine, Thomas J.

AU - Frisardi, Vincenza

AU - Diez-Fairen, Monica

AU - Rivadeneira, Fernando

AU - Petersen, Ronald C.

AU - Deramecourt, Vincent

AU - Alvarez, Ignacio

AU - Salani, Francesca

AU - Ciaramella, Antonio

AU - Boerwinkle, Eric

AU - Reiman, Eric M.

AU - Fievet, Nathalie

AU - Rotter, Jerome I.

AU - Reisch, Joan S.

AU - Hanon, Olivier

AU - Cupidi, Chiara

AU - Andre Uitterlinden, A. G.

AU - Royall, Donald R.

AU - Dufouil, Carole

AU - Maletta, Raffaele Giovanni

AU - de Rojas, Itziar

AU - Sano, Mary

AU - Brice, Alexis

AU - Cecchetti, Roberta

AU - George-Hyslop, Peter St

AU - Ritchie, Karen

AU - Tsolaki, Magda

AU - Tsuang, Debby W.

AU - Dubois, Bruno

AU - Craig, David

AU - Wu, Chuang Kuo

AU - Soininen, Hilkka

AU - Avramidou, Despoina

AU - Albin, Roger L.

AU - Fratiglioni, Laura

AU - Germanou, Antonia

AU - Apostolova, Liana G.

AU - Keller, Lina

AU - Koutroumani, Maria

AU - Arnold, Steven E.

AU - Panza, Francesco

AU - Gkatzima, Olymbia

AU - Asthana, Sanjay

AU - Hannequin, Didier

AU - Whitehead, Patrice

AU - Atwood, Craig S.

AU - Caffarra, Paolo

AU - Hampel, Harald

AU - Quintela, Inés

AU - Carracedo, Ángel

AU - Lannfelt, Lars

AU - Rubinsztein, David C.

AU - Barnes, Lisa L.

AU - Pasquier, Florence

AU - Frölich, Lutz

AU - Barral, Sandra

AU - McGuinness, Bernadette

AU - Beach, Thomas G.

AU - Johnston, Janet A.

AU - Becker, James T.

AU - Passmore, Peter

AU - Bigio, Eileen H.

AU - Schott, Jonathan M.

AU - Bird, Thomas D.

AU - Warren, Jason D.

AU - Boeve, Bradley F.

AU - Lupton, Michelle K.

AU - Bowen, James D.

AU - Proitsi, Petra

AU - Boxer, Adam

AU - Powell, John F.

AU - Burke, James R.

AU - Kauwe, John S.K.

AU - Burns, Jeffrey M.

AU - Mancuso, Michelangelo

AU - Buxbaum, Joseph D.

AU - Bonuccelli, Ubaldo

AU - Cairns, Nigel J.

AU - McQuillin, Andrew

AU - Cao, Chuanhai

AU - Livingston, Gill

AU - Carlson, Chris S.

AU - Bass, Nicholas J.

AU - Carlsson, Cynthia M.

AU - Hardy, John

AU - Carney, Regina M.

AU - Bras, Jose

AU - Carrasquillo, Minerva M.

AU - Guerreiro, Rita

AU - Allen, Mariet

AU - Chui, Helena C.

AU - Fisher, Elizabeth

AU - Masullo, Carlo

AU - Crocco, Elizabeth A.

AU - DeCarli, Charles

AU - Bisceglio, Gina

AU - Dick, Malcolm

AU - Ma, Li

AU - Duara, Ranjan

AU - Graff-Radford, Neill R.

AU - Evans, Denis A.

AU - Hodges, Angela

AU - Faber, Kelley M.

AU - Scherer, Martin

AU - Fallon, Kenneth B.

AU - Riemenschneider, Matthias

AU - Fardo, David W.

AU - Heun, Reinhard

AU - Farlow, Martin R.

AU - Kölsch, Heike

AU - Ferris, Steven

AU - Leber, Markus

AU - Foroud, Tatiana M.

AU - Heuser, Isabella

AU - Galasko, Douglas R.

AU - Giegling, Ina

AU - Gearing, Marla

AU - Hüll, Michael

AU - Geschwind, Daniel H.

AU - Gilbert, John R.

AU - Morris, John C.

AU - Green, Robert C.

AU - Mayo, Kevin

AU - Growdon, John H.

AU - Feulner, Thomas

AU - Hamilton, Ronald L.

AU - Harrell, Lindy E.

AU - Drichel, Dmitriy

AU - Honig, Lawrence S.

AU - Cushion, Thomas D.

AU - Huentelman, Matthew J.

AU - Hollingworth, Paul

AU - Hulette, Christine M.

AU - Hyman, Bradley T.

AU - Marshall, Rachel

AU - Jarvik, Gail P.

AU - Meggy, Alun

AU - Abner, Erin

AU - Menzies, Georgina E.

AU - Jin, Lee Way

AU - Leonenko, Ganna

AU - Real, Luis M.

AU - Jun, Gyungah R.

AU - Baldwin, Clinton T.

AU - Grozeva, Detelina

AU - Karydas, Anna

AU - Russo, Giancarlo

AU - Kaye, Jeffrey A.

AU - Kim, Ronald

AU - Jessen, Frank

AU - Kowall, Neil W.

AU - Vellas, Bruno

AU - Kramer, Joel H.

AU - Vardy, Emma

AU - LaFerla, Frank M.

AU - Jöckel, Karl Heinz

AU - Lah, James J.

AU - Dichgans, Martin

AU - Leverenz, James B.

AU - Mann, David

AU - Levey, Allan I.

AU - Pickering-Brown, Stuart

AU - Lieberman, Andrew P.

AU - Klopp, Norman

AU - Lunetta, Kathryn L.

AU - Wichmann, H. Erich

AU - Lyketsos, Constantine G.

AU - Morgan, Kevin

AU - Marson, Daniel C.

AU - Brown, Kristelle

AU - Martiniuk, Frank

AU - Medway, Christopher

AU - Mash, Deborah C.

AU - Nöthen, Markus M.

AU - Masliah, Eliezer

AU - Hooper, Nigel M.

AU - McCormick, Wayne C.

AU - Daniele, Antonio

AU - McCurry, Susan M.

AU - Bayer, Anthony

AU - McDavid, Andrew N.

AU - Gallacher, John

AU - McKee, Ann C.

AU - van den Bussche, Hendrik

AU - Mesulam, Marsel

AU - Brayne, Carol

AU - Miller, Bruce L.

AU - Riedel-Heller, Steffi

AU - Miller, Carol A.

AU - Miller, Joshua W.

AU - Al-Chalabi, Ammar

AU - Morris, John C.

AU - Shaw, Christopher E.

AU - Myers, Amanda J.

AU - Wiltfang, Jens

AU - O’Bryant, Sid

AU - Olichney, John M.

AU - Alvarez, Victoria

AU - Parisi, Joseph E.

AU - Singleton, Andrew B.

AU - Paulson, Henry L.

AU - Collinge, John

AU - Perry, William R.

AU - Mead, Simon

AU - Peskind, Elaine

AU - Cribbs, David H.

AU - Rossor, Martin

AU - Pierce, Aimee

AU - Ryan, Natalie S.

AU - Poon, Wayne W.

AU - Nacmias, Benedetta

AU - Potter, Huntington

AU - Sorbi, Sandro

AU - Quinn, Joseph G.

AU - Sacchinelli, Eleonora

AU - Raj, Ashok

AU - Spalletta, Gianfranco

AU - Raskind, Murray

AU - Caltagirone, Carlo

AU - Bossù, Paola

AU - Orfei, Maria Donata

AU - Reisberg, Barry

AU - Clarke, Robert

AU - Reitz, Christiane

AU - Smith, A. David

AU - Ringman, John M.

AU - Warden, Donald

AU - Roberson, Erik D.

AU - Wilcock, Gordon

AU - Rogaeva, Ekaterina

AU - Bruni, Amalia Cecilia

AU - Rosen, Howard J.

AU - Gallo, Maura

AU - Rosenberg, Roger N.

AU - Ben-Shlomo, Yoav

AU - Sager, Mark A.

AU - Mecocci, Patrizia

AU - Saykin, Andrew J.

AU - Pastor, Pau

AU - Cuccaro, Michael L.

AU - Vance, Jeffery M.

AU - Schneider, Julie A.

AU - Schneider, Lori S.

AU - Slifer, Susan

AU - Seeley, William W.

AU - Smith, Amanda G.

AU - Sonnen, Joshua A.

AU - Spina, Salvatore

AU - Stern, Robert A.

AU - Swerdlow, Russell H.

AU - Tang, Mitchell

AU - Tanzi, Rudolph E.

AU - Trojanowski, John Q.

AU - Troncoso, Juan C.

AU - Van Deerlin, Vivianna M.

AU - Van Eldik, Linda J.

AU - Vinters, Harry V.

AU - Vonsattel, Jean Paul

AU - Weintraub, Sandra

AU - Welsh-Bohmer, Kathleen A.

AU - Wilhelmsen, Kirk C.

AU - Williamson, Jennifer

AU - Wingo, Thomas S.

AU - Woltjer, Randall L.

AU - Wright, Clinton B.

AU - Yu, Chang En

AU - Yu, Lei

AU - Saba, Yasaman

AU - Pilotto, Alberto

AU - Bullido, Maria J.

AU - Peters, Oliver

AU - Crane, Paul K.

AU - Bennett, David

AU - Bosco, Paola

AU - Coto, Eliecer

AU - Boccardi, Virginia

AU - De Jager, Phil L.

AU - Lleo, Alberto

AU - Warner, Nick

AU - Lopez, Oscar L.

AU - Ingelsson, Martin

AU - Deloukas, Panagiotis

AU - Cruchaga, Carlos

AU - Graff, Caroline

AU - Gwilliam, Rhian

AU - Fornage, Myriam

AU - Goate, Alison M.

AU - Sanchez-Juan, Pascual

AU - Kehoe, Patrick G.

AU - Amin, Najaf

AU - Ertekin-Taner, Nilifur

AU - Berr, Claudine

AU - Debette, Stéphanie

AU - Love, Seth

AU - Launer, Lenore J.

AU - Younkin, Steven G.

AU - Dartigues, Jean Francois

AU - Corcoran, Chris

AU - Ikram, M. Arfan

AU - Dickson, Dennis W.

AU - Nicolas, Gael

AU - Campion, Dominique

AU - Tschanz, Jo Ann

AU - Schmidt, Helena

AU - Hakonarson, Hakon

AU - Clarimon, Jordi

AU - Munger, Ron

AU - Schmidt, Reinhold

AU - Farrer, Lindsay A.

AU - Van Broeckhoven, Christine

AU - C. O’Donovan, Michael

AU - DeStefano, Anita L.

AU - Jones, Lesley

AU - Haines, Jonathan L.

AU - Deleuze, Jean Francois

AU - Owen, Michael J.

AU - Gudnason, Vilmundur

AU - Mayeux, Richard

AU - Escott-Price, Valentina

AU - Psaty, Bruce M.

AU - Ramirez, Alfredo

AU - Wang, Li San

AU - Ruiz, Agustin

AU - van Duijn, Cornelia M.

AU - Holmans, Peter A.

AU - Seshadri, Sudha

AU - Williams, Julie

AU - Amouyel, Phillippe

AU - Schellenberg, Gerard D.

AU - Lambert, Jean Charles

AU - Pericak-Vance, Margaret A.

PY - 2019/2/28

Y1 - 2019/2/28

N2 - 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 Aβ 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.

AB - 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 Aβ 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.

UR - http://www.mendeley.com/research/genetic-metaanalysis-diagnosed-alzheimers-disease-identifies-new-risk-loci-implicates-a%CE%B2-tau-immunit

U2 - 10.1038/s41588-019-0358-2

DO - 10.1038/s41588-019-0358-2

M3 - Article

C2 - 30820047

VL - 51

SP - 414

EP - 430

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 3

ER -