%0 Journal Article %J Nat Commun %D 2023 %T Author Correction: Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. %A de Rojas, Itziar %A Moreno-Grau, Sonia %A Tesi, Niccolo %A Grenier-Boley, Benjamin %A Andrade, Victor %A Jansen, Iris E %A Pedersen, Nancy L %A Stringa, Najada %A Zettergren, Anna %A Hernández, Isabel %A Montrreal, Laura %A Antúnez, Carmen %A Antonell, Anna %A Tankard, Rick M %A Bis, Joshua C %A Sims, Rebecca %A Bellenguez, Céline %A Quintela, Inés %A González-Perez, Antonio %A Calero, Miguel %A Franco-Macías, Emilio %A Macías, Juan %A Blesa, Rafael %A Cervera-Carles, Laura %A Menéndez-González, Manuel %A Frank-García, Ana %A Royo, Jose Luís %A Moreno, Fermin %A Huerto Vilas, Raquel %A Baquero, Miquel %A Diez-Fairen, Monica %A Lage, Carmen %A García-Madrona, Sebastián %A García-González, Pablo %A Alarcón-Martín, Emilio %A Valero, Sergi %A Sotolongo-Grau, Oscar %A Ullgren, Abbe %A Naj, Adam C %A Lemstra, Afina W %A Benaque, Alba %A Pérez-Cordón, Alba %A Benussi, Alberto %A Rábano, Alberto %A Padovani, Alessandro %A Squassina, Alessio %A de Mendonça, Alexandre %A Arias Pastor, Alfonso %A Kok, Almar A L %A Meggy, Alun %A Pastor, Ana Belén %A Espinosa, Ana %A Corma-Gómez, Anaïs %A Martín Montes, Angel %A Sanabria, Ángela %A DeStefano, Anita L %A Schneider, Anja %A Haapasalo, Annakaisa %A Kinhult Ståhlbom, Anne %A Tybjærg-Hansen, Anne %A Hartmann, Annette M %A Spottke, Annika %A Corbatón-Anchuelo, Arturo %A Rongve, Arvid %A Borroni, Barbara %A Arosio, Beatrice %A Nacmias, Benedetta %A Nordestgaard, Børge G %A Kunkle, Brian W %A Charbonnier, Camille %A Abdelnour, Carla %A Masullo, Carlo %A Martínez Rodríguez, Carmen %A Muñoz-Fernandez, Carmen %A Dufouil, Carole %A Graff, Caroline %A Ferreira, Catarina B %A Chillotti, Caterina %A Reynolds, Chandra A %A Fenoglio, Chiara %A Van Broeckhoven, Christine %A Clark, Christopher %A Pisanu, Claudia %A Satizabal, Claudia L %A Holmes, Clive %A Buiza-Rueda, Dolores %A Aarsland, Dag %A Rujescu, Dan %A Alcolea, Daniel %A Galimberti, Daniela %A Wallon, David %A Seripa, Davide %A Grünblatt, Edna %A Dardiotis, Efthimios %A Düzel, Emrah %A Scarpini, Elio %A Conti, Elisa %A Rubino, Elisa %A Gelpi, Ellen %A Rodriguez-Rodriguez, Eloy %A Duron, Emmanuelle %A Eric Boerwinkle %A Ferri, Evelyn %A Tagliavini, Fabrizio %A Küçükali, Fahri %A Pasquier, Florence %A Sanchez-Garcia, Florentino %A Mangialasche, Francesca %A Jessen, Frank %A Nicolas, Gaël %A Selbæk, Geir %A Ortega, Gemma %A Chêne, Geneviève %A Hadjigeorgiou, Georgios %A Rossi, Giacomina %A Spalletta, Gianfranco %A Giaccone, Giorgio %A Grande, Giulia %A Binetti, Giuliano %A Papenberg, Goran %A Hampel, Harald %A Bailly, Henri %A Zetterberg, Henrik %A Soininen, Hilkka %A Karlsson, Ida K %A Alvarez, Ignacio %A Appollonio, Ildebrando %A Giegling, Ina %A Skoog, Ingmar %A Saltvedt, Ingvild %A Rainero, Innocenzo %A Rosas Allende, Irene %A Hort, Jakub %A Diehl-Schmid, Janine %A Van Dongen, Jasper %A Vidal, Jean-Sebastien %A Lehtisalo, Jenni %A Wiltfang, Jens %A Thomassen, Jesper Qvist %A Kornhuber, Johannes %A Haines, Jonathan L %A Vogelgsang, Jonathan %A Pineda, Juan A %A Fortea, Juan %A Popp, Julius %A Deckert, Jürgen %A Buerger, Katharina %A Morgan, Kevin %A Fließbach, Klaus %A Sleegers, Kristel %A Molina-Porcel, Laura %A Kilander, Lena %A Weinhold, Leonie %A Farrer, Lindsay A %A Wang, Li-San %A Kleineidam, Luca %A Farotti, Lucia %A Parnetti, Lucilla %A Tremolizzo, Lucio %A Hausner, Lucrezia %A Benussi, Luisa %A Froelich, Lutz %A Ikram, M Arfan %A Deniz-Naranjo, M Candida %A Tsolaki, Magda %A Rosende-Roca, Maitée %A Löwenmark, Malin %A Hulsman, Marc %A Spallazzi, Marco %A Pericak-Vance, Margaret A %A Esiri, Margaret %A Bernal Sánchez-Arjona, María %A Dalmasso, Maria Carolina %A Martínez-Larrad, María Teresa %A Arcaro, Marina %A Nöthen, Markus M %A Fernández-Fuertes, Marta %A Dichgans, Martin %A Ingelsson, Martin %A Herrmann, Martin J %A Scherer, Martin %A Vyhnalek, Martin %A Kosmidis, Mary H %A Yannakoulia, Mary %A Schmid, Matthias %A Ewers, Michael %A Heneka, Michael T %A Wagner, Michael %A Scamosci, Michela %A Kivipelto, Miia %A Hiltunen, Mikko %A Zulaica, Miren %A Alegret, Montserrat %A Fornage, Myriam %A Roberto, Natalia %A van Schoor, Natasja M %A Seidu, Nazib M %A Banaj, Nerisa %A Armstrong, Nicola J %A Scarmeas, Nikolaos %A Scherbaum, Norbert %A Goldhardt, Oliver %A Hanon, Oliver %A Peters, Oliver %A Skrobot, Olivia Anna %A Quenez, Olivier %A Lerch, Ondrej %A Bossù, Paola %A Caffarra, Paolo %A Dionigi Rossi, Paolo %A Sakka, Paraskevi %A Mecocci, Patrizia %A Hoffmann, Per %A Holmans, Peter A %A Fischer, Peter %A Riederer, Peter %A Yang, Qiong %A Marshall, Rachel %A Kalaria, Rajesh N %A Mayeux, Richard %A Vandenberghe, Rik %A Cecchetti, Roberta %A Ghidoni, Roberta %A Frikke-Schmidt, Ruth %A Sorbi, Sandro %A Hägg, Sara %A Engelborghs, Sebastiaan %A Helisalmi, Seppo %A Botne Sando, Sigrid %A Kern, Silke %A Archetti, Silvana %A Boschi, Silvia %A Fostinelli, Silvia %A Gil, Silvia %A Mendoza, Silvia %A Mead, Simon %A Ciccone, Simona %A Djurovic, Srdjan %A Heilmann-Heimbach, Stefanie %A Riedel-Heller, Steffi %A Kuulasmaa, Teemu %A Del Ser, Teodoro %A Lebouvier, Thibaud %A Polak, Thomas %A Ngandu, Tiia %A Grimmer, Timo %A Bessi, Valentina %A Escott-Price, Valentina %A Giedraitis, Vilmantas %A Deramecourt, Vincent %A Maier, Wolfgang %A Jian, Xueqiu %A Pijnenburg, Yolande A L %A Kehoe, Patrick Gavin %A Garcia-Ribas, Guillermo %A Sánchez-Juan, Pascual %A Pastor, Pau %A Pérez-Tur, Jordi %A Piñol-Ripoll, Gerard %A Lopez de Munain, Adolfo %A García-Alberca, Jose María %A Bullido, María J %A Alvarez, Victoria %A Lleo, Alberto %A Real, Luis M %A Mir, Pablo %A Medina, Miguel %A Scheltens, Philip %A Holstege, Henne %A Marquié, Marta %A Sáez, María Eugenia %A Carracedo, Ángel %A Amouyel, Philippe %A Schellenberg, Gerard D %A Williams, Julie %A Seshadri, Sudha %A van Duijn, Cornelia M %A Mather, Karen A %A Sánchez-Valle, Raquel %A Serrano-Ríos, Manuel %A Orellana, Adelina %A Tarraga, Lluis %A Blennow, Kaj %A Huisman, Martijn %A Andreassen, Ole A %A Posthuma, Danielle %A Clarimon, Jordi %A Boada, Mercè %A van der Flier, Wiesje M %A Ramirez, Alfredo %A Lambert, Jean-Charles %A van der Lee, Sven J %A Ruiz, Agustin %B Nat Commun %V 14 %P 716 %8 2023 Feb 09 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/36759603?dopt=Abstract %R 10.1038/s41467-023-36192-x %0 Journal Article %J Nat Commun %D 2021 %T Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. %A de Rojas, Itziar %A Moreno-Grau, Sonia %A Tesi, Niccolo %A Grenier-Boley, Benjamin %A Andrade, Victor %A Jansen, Iris E %A Pedersen, Nancy L %A Stringa, Najada %A Zettergren, Anna %A Hernández, Isabel %A Montrreal, Laura %A Antúnez, Carmen %A Antonell, Anna %A Tankard, Rick M %A Bis, Joshua C %A Sims, Rebecca %A Bellenguez, Céline %A Quintela, Inés %A González-Perez, Antonio %A Calero, Miguel %A Franco-Macías, Emilio %A Macías, Juan %A Blesa, Rafael %A Cervera-Carles, Laura %A Menéndez-González, Manuel %A Frank-García, Ana %A Royo, Jose Luís %A Moreno, Fermin %A Huerto Vilas, Raquel %A Baquero, Miquel %A Diez-Fairen, Monica %A Lage, Carmen %A García-Madrona, Sebastián %A García-González, Pablo %A Alarcón-Martín, Emilio %A Valero, Sergi %A Sotolongo-Grau, Oscar %A Ullgren, Abbe %A Naj, Adam C %A Lemstra, Afina W %A Benaque, Alba %A Pérez-Cordón, Alba %A Benussi, Alberto %A Rábano, Alberto %A Padovani, Alessandro %A Squassina, Alessio %A de Mendonça, Alexandre %A Arias Pastor, Alfonso %A Kok, Almar A L %A Meggy, Alun %A Pastor, Ana Belén %A Espinosa, Ana %A Corma-Gómez, Anaïs %A Martín Montes, Angel %A Sanabria, Ángela %A DeStefano, Anita L %A Schneider, Anja %A Haapasalo, Annakaisa %A Kinhult Ståhlbom, Anne %A Tybjærg-Hansen, Anne %A Hartmann, Annette M %A Spottke, Annika %A Corbatón-Anchuelo, Arturo %A Rongve, Arvid %A Borroni, Barbara %A Arosio, Beatrice %A Nacmias, Benedetta %A Nordestgaard, Børge G %A Kunkle, Brian W %A Charbonnier, Camille %A Abdelnour, Carla %A Masullo, Carlo %A Martínez Rodríguez, Carmen %A Muñoz-Fernandez, Carmen %A Dufouil, Carole %A Graff, Caroline %A Ferreira, Catarina B %A Chillotti, Caterina %A Reynolds, Chandra A %A Fenoglio, Chiara %A Van Broeckhoven, Christine %A Clark, Christopher %A Pisanu, Claudia %A Satizabal, Claudia L %A Holmes, Clive %A Buiza-Rueda, Dolores %A Aarsland, Dag %A Rujescu, Dan %A Alcolea, Daniel %A Galimberti, Daniela %A Wallon, David %A Seripa, Davide %A Grünblatt, Edna %A Dardiotis, Efthimios %A Düzel, Emrah %A Scarpini, Elio %A Conti, Elisa %A Rubino, Elisa %A Gelpi, Ellen %A Rodriguez-Rodriguez, Eloy %A Duron, Emmanuelle %A Eric Boerwinkle %A Ferri, Evelyn %A Tagliavini, Fabrizio %A Küçükali, Fahri %A Pasquier, Florence %A Sanchez-Garcia, Florentino %A Mangialasche, Francesca %A Jessen, Frank %A Nicolas, Gaël %A Selbæk, Geir %A Ortega, Gemma %A Chêne, Geneviève %A Hadjigeorgiou, Georgios %A Rossi, Giacomina %A Spalletta, Gianfranco %A Giaccone, Giorgio %A Grande, Giulia %A Binetti, Giuliano %A Papenberg, Goran %A Hampel, Harald %A Bailly, Henri %A Zetterberg, Henrik %A Soininen, Hilkka %A Karlsson, Ida K %A Alvarez, Ignacio %A Appollonio, Ildebrando %A Giegling, Ina %A Skoog, Ingmar %A Saltvedt, Ingvild %A Rainero, Innocenzo %A Rosas Allende, Irene %A Hort, Jakub %A Diehl-Schmid, Janine %A Van Dongen, Jasper %A Vidal, Jean-Sebastien %A Lehtisalo, Jenni %A Wiltfang, Jens %A Thomassen, Jesper Qvist %A Kornhuber, Johannes %A Haines, Jonathan L %A Vogelgsang, Jonathan %A Pineda, Juan A %A Fortea, Juan %A Popp, Julius %A Deckert, Jürgen %A Buerger, Katharina %A Morgan, Kevin %A Fließbach, Klaus %A Sleegers, Kristel %A Molina-Porcel, Laura %A Kilander, Lena %A Weinhold, Leonie %A Farrer, Lindsay A %A Wang, Li-San %A Kleineidam, Luca %A Farotti, Lucia %A Parnetti, Lucilla %A Tremolizzo, Lucio %A Hausner, Lucrezia %A Benussi, Luisa %A Froelich, Lutz %A Ikram, M Arfan %A Deniz-Naranjo, M Candida %A Tsolaki, Magda %A Rosende-Roca, Maitée %A Löwenmark, Malin %A Hulsman, Marc %A Spallazzi, Marco %A Pericak-Vance, Margaret A %A Esiri, Margaret %A Bernal Sánchez-Arjona, María %A Dalmasso, Maria Carolina %A Martínez-Larrad, María Teresa %A Arcaro, Marina %A Nöthen, Markus M %A Fernández-Fuertes, Marta %A Dichgans, Martin %A Ingelsson, Martin %A Herrmann, Martin J %A Scherer, Martin %A Vyhnalek, Martin %A Kosmidis, Mary H %A Yannakoulia, Mary %A Schmid, Matthias %A Ewers, Michael %A Heneka, Michael T %A Wagner, Michael %A Scamosci, Michela %A Kivipelto, Miia %A Hiltunen, Mikko %A Zulaica, Miren %A Alegret, Montserrat %A Fornage, Myriam %A Roberto, Natalia %A van Schoor, Natasja M %A Seidu, Nazib M %A Banaj, Nerisa %A Armstrong, Nicola J %A Scarmeas, Nikolaos %A Scherbaum, Norbert %A Goldhardt, Oliver %A Hanon, Oliver %A Peters, Oliver %A Skrobot, Olivia Anna %A Quenez, Olivier %A Lerch, Ondrej %A Bossù, Paola %A Caffarra, Paolo %A Dionigi Rossi, Paolo %A Sakka, Paraskevi %A Mecocci, Patrizia %A Hoffmann, Per %A Holmans, Peter A %A Fischer, Peter %A Riederer, Peter %A Yang, Qiong %A Marshall, Rachel %A Kalaria, Rajesh N %A Mayeux, Richard %A Vandenberghe, Rik %A Cecchetti, Roberta %A Ghidoni, Roberta %A Frikke-Schmidt, Ruth %A Sorbi, Sandro %A Hägg, Sara %A Engelborghs, Sebastiaan %A Helisalmi, Seppo %A Botne Sando, Sigrid %A Kern, Silke %A Archetti, Silvana %A Boschi, Silvia %A Fostinelli, Silvia %A Gil, Silvia %A Mendoza, Silvia %A Mead, Simon %A Ciccone, Simona %A Djurovic, Srdjan %A Heilmann-Heimbach, Stefanie %A Riedel-Heller, Steffi %A Kuulasmaa, Teemu %A Del Ser, Teodoro %A Lebouvier, Thibaud %A Polak, Thomas %A Ngandu, Tiia %A Grimmer, Timo %A Bessi, Valentina %A Escott-Price, Valentina %A Giedraitis, Vilmantas %A Deramecourt, Vincent %A Maier, Wolfgang %A Jian, Xueqiu %A Pijnenburg, Yolande A L %A Kehoe, Patrick Gavin %A Garcia-Ribas, Guillermo %A Sánchez-Juan, Pascual %A Pastor, Pau %A Pérez-Tur, Jordi %A Piñol-Ripoll, Gerard %A Lopez de Munain, Adolfo %A García-Alberca, Jose María %A Bullido, María J %A Alvarez, Victoria %A Lleo, Alberto %A Real, Luis M %A Mir, Pablo %A Medina, Miguel %A Scheltens, Philip %A Holstege, Henne %A Marquié, Marta %A Sáez, María Eugenia %A Carracedo, Ángel %A Amouyel, Philippe %A Schellenberg, Gerard D %A Williams, Julie %A Seshadri, Sudha %A van Duijn, Cornelia M %A Mather, Karen A %A Sánchez-Valle, Raquel %A Serrano-Ríos, Manuel %A Orellana, Adelina %A Tarraga, Lluis %A Blennow, Kaj %A Huisman, Martijn %A Andreassen, Ole A %A Posthuma, Danielle %A Clarimon, Jordi %A Boada, Mercè %A van der Flier, Wiesje M %A Ramirez, Alfredo %A Lambert, Jean-Charles %A van der Lee, Sven J %A Ruiz, Agustin %K Age of Onset %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Amyloid beta-Protein Precursor %K Apolipoproteins E %K Case-Control Studies %K Cohort Studies %K Datasets as Topic %K Female %K Follow-Up Studies %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Heterozygote %K Humans %K Male %K Middle Aged %K Multifactorial Inheritance %K Polymorphism, Single Nucleotide %K Risk Assessment %K Risk Factors %X

Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease.

%B Nat Commun %V 12 %P 3417 %8 2021 Jun 07 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/34099642?dopt=Abstract %R 10.1038/s41467-021-22491-8 %0 Journal Article %J Nat Genet %D 2019 %T Author Correction: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. %A Kunkle, Brian W %A Grenier-Boley, Benjamin %A Sims, Rebecca %A Bis, Joshua C %A Damotte, Vincent %A Naj, Adam C %A Boland, Anne %A Vronskaya, Maria %A van der Lee, Sven J %A Amlie-Wolf, Alexandre %A Bellenguez, Céline %A Frizatti, Aura %A Chouraki, Vincent %A Martin, Eden R %A Sleegers, Kristel %A Badarinarayan, Nandini %A Jakobsdottir, Johanna %A Hamilton-Nelson, Kara L %A Moreno-Grau, Sonia %A Olaso, Robert %A Raybould, Rachel %A Chen, Yuning %A Kuzma, Amanda B %A Hiltunen, Mikko %A Morgan, Taniesha %A Ahmad, Shahzad %A Vardarajan, Badri N %A Epelbaum, Jacques %A Hoffmann, Per %A Boada, Mercè %A Beecham, Gary W %A Garnier, Jean-Guillaume %A Harold, Denise %A Fitzpatrick, Annette L %A Valladares, Otto %A Moutet, Marie-Laure %A Gerrish, Amy %A Smith, Albert V %A Qu, Liming %A Bacq, Delphine %A Denning, Nicola %A Jian, Xueqiu %A Zhao, Yi %A Del Zompo, Maria %A Fox, Nick C %A Choi, Seung-Hoan %A Mateo, Ignacio %A Hughes, Joseph T %A Adams, Hieab H %A Malamon, John %A Sanchez-Garcia, Florentino %A Patel, Yogen %A Brody, Jennifer A %A Dombroski, Beth A %A Naranjo, Maria Candida Deniz %A Daniilidou, Makrina %A Eiriksdottir, Gudny %A Mukherjee, Shubhabrata %A Wallon, David %A Uphill, James %A Aspelund, Thor %A Cantwell, Laura B %A Garzia, Fabienne %A Galimberti, Daniela %A Hofer, Edith %A Butkiewicz, Mariusz %A Fin, Bertrand %A Scarpini, Elio %A Sarnowski, Chloe %A Bush, Will S %A Meslage, Stéphane %A Kornhuber, Johannes %A White, Charles C %A Song, Yuenjoo %A Barber, Robert C %A Engelborghs, Sebastiaan %A Sordon, Sabrina %A Voijnovic, Dina %A Adams, Perrie M %A Vandenberghe, Rik %A Mayhaus, Manuel %A Cupples, L Adrienne %A 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%A Bisceglio, Gina %A Dick, Malcolm %A Ma, Li %A Duara, Ranjan %A Graff-Radford, Neill R %A Evans, Denis A %A Hodges, Angela %A Faber, Kelley M %A Scherer, Martin %A Fallon, Kenneth B %A Riemenschneider, Matthias %A Fardo, David W %A Heun, Reinhard %A Farlow, Martin R %A Kölsch, Heike %A Ferris, Steven %A Leber, Markus %A Foroud, Tatiana M %A Heuser, Isabella %A Galasko, Douglas R %A Giegling, Ina %A Gearing, Marla %A Hüll, Michael %A Geschwind, Daniel H %A Gilbert, John R %A Morris, John %A Green, Robert C %A Mayo, Kevin %A Growdon, John H %A Feulner, Thomas %A Hamilton, Ronald L %A Harrell, Lindy E %A Drichel, Dmitriy %A Honig, Lawrence S %A Cushion, Thomas D %A Huentelman, Matthew J %A Hollingworth, Paul %A Hulette, Christine M %A Hyman, Bradley T %A Marshall, Rachel %A Jarvik, Gail P %A Meggy, Alun %A Abner, Erin %A Menzies, Georgina E %A Jin, Lee-Way %A Leonenko, Ganna %A Real, Luis M %A Jun, Gyungah R %A Baldwin, Clinton T %A Grozeva, Detelina %A Karydas, Anna %A Russo, Giancarlo %A Kaye, Jeffrey A %A Kim, Ronald %A Jessen, Frank %A Kowall, Neil W %A Vellas, Bruno %A Kramer, Joel H %A Vardy, Emma %A LaFerla, Frank M %A Jöckel, Karl-Heinz %A Lah, James J %A Dichgans, Martin %A Leverenz, James B %A Mann, David %A Levey, Allan I %A Pickering-Brown, Stuart %A Lieberman, Andrew P %A Klopp, Norman %A Lunetta, Kathryn L %A Wichmann, H-Erich %A Lyketsos, Constantine G %A Morgan, Kevin %A Marson, Daniel C %A Brown, Kristelle %A Martiniuk, Frank %A Medway, Christopher %A Mash, Deborah C %A Nöthen, Markus M %A Masliah, Eliezer %A Hooper, Nigel M %A McCormick, Wayne C %A Daniele, Antonio %A McCurry, Susan M %A Bayer, Anthony %A McDavid, Andrew N %A Gallacher, John %A McKee, Ann C %A van den Bussche, Hendrik %A Mesulam, Marsel %A Brayne, Carol %A Miller, Bruce L %A Riedel-Heller, Steffi %A Miller, Carol A %A Miller, Joshua W %A Al-Chalabi, Ammar %A Morris, John C %A Shaw, Christopher E %A Myers, Amanda J %A Wiltfang, Jens %A O'Bryant, Sid %A Olichney, John M %A Alvarez, Victoria %A Parisi, Joseph E %A Singleton, Andrew B %A Paulson, Henry L %A Collinge, John %A Perry, William R %A Mead, Simon %A Peskind, Elaine %A Cribbs, David H %A Rossor, Martin %A Pierce, Aimee %A Ryan, Natalie S %A Poon, Wayne W %A Nacmias, Benedetta %A Potter, Huntington %A Sorbi, Sandro %A Quinn, Joseph F %A Sacchinelli, Eleonora %A Raj, Ashok %A Spalletta, Gianfranco %A Raskind, Murray %A Caltagirone, Carlo %A Bossù, Paola %A Orfei, Maria Donata %A Reisberg, Barry %A Clarke, Robert %A Reitz, Christiane %A Smith, A David %A Ringman, John M %A Warden, Donald %A Roberson, Erik D %A Wilcock, Gordon %A Rogaeva, Ekaterina %A Bruni, Amalia Cecilia %A Rosen, Howard J %A Gallo, Maura %A Rosenberg, Roger N %A Ben-Shlomo, Yoav %A Sager, Mark A %A Mecocci, Patrizia %A Saykin, Andrew J %A Pastor, Pau %A Cuccaro, Michael L %A Vance, Jeffery M %A Schneider, Julie A %A Schneider, Lori S %A Slifer, Susan %A Seeley, William W %A Smith, Amanda G %A Sonnen, Joshua A %A Spina, Salvatore %A Stern, Robert A %A Swerdlow, Russell H %A Tang, Mitchell %A Tanzi, Rudolph E %A Trojanowski, John Q %A Troncoso, Juan C %A Van Deerlin, Vivianna M %A Van Eldik, Linda J %A Vinters, Harry V %A Vonsattel, Jean Paul %A Weintraub, Sandra %A Welsh-Bohmer, Kathleen A %A Wilhelmsen, Kirk C %A Williamson, Jennifer %A Wingo, Thomas S %A Woltjer, Randall L %A Wright, Clinton B %A Yu, Chang-En %A Yu, Lei %A Saba, Yasaman %A Pilotto, Alberto %A Bullido, María J %A Peters, Oliver %A Crane, Paul K %A Bennett, David %A Bosco, Paola %A Coto, Eliecer %A Boccardi, Virginia %A De Jager, Phil L %A Lleo, Alberto %A Warner, Nick %A Lopez, Oscar L %A Ingelsson, Martin %A Deloukas, Panagiotis %A Cruchaga, Carlos %A Graff, Caroline %A Gwilliam, Rhian %A Fornage, Myriam %A Goate, Alison M %A Sánchez-Juan, Pascual %A Kehoe, Patrick G %A Amin, Najaf %A Ertekin-Taner, Nilifur %A Berr, Claudine %A Debette, Stephanie %A Love, Seth %A Launer, Lenore J %A Younkin, Steven G %A Dartigues, Jean-François %A Corcoran, Chris %A Ikram, M Arfan %A Dickson, Dennis W %A Nicolas, Gaël %A Campion, Dominique %A Tschanz, JoAnn %A Schmidt, Helena %A Hakonarson, Hakon %A Clarimon, Jordi %A Munger, Ron %A Schmidt, Reinhold %A Farrer, Lindsay A %A Van Broeckhoven, Christine %A O'Donovan, Michael C %A DeStefano, Anita L %A Jones, Lesley %A Haines, Jonathan L %A Deleuze, Jean-François %A Owen, Michael J %A Gudnason, Vilmundur %A Mayeux, Richard %A Escott-Price, Valentina %A Psaty, Bruce M %A Ramirez, Alfredo %A Wang, Li-San %A Ruiz, Agustin %A van Duijn, Cornelia M %A Holmans, Peter A %A Seshadri, Sudha %A Williams, Julie %A Amouyel, Phillippe %A Schellenberg, Gerard D %A Lambert, Jean-Charles %A Pericak-Vance, Margaret A %X

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

%B Nat Genet %V 51 %P 1423-1424 %8 2019 Sep %G eng %N 9 %1 https://www.ncbi.nlm.nih.gov/pubmed/31417202?dopt=Abstract %R 10.1038/s41588-019-0495-7 %0 Journal Article %J Nat Genet %D 2019 %T Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. %A Kunkle, Brian W %A Grenier-Boley, Benjamin %A Sims, Rebecca %A Bis, Joshua C %A Damotte, Vincent %A Naj, Adam C %A Boland, Anne %A Vronskaya, Maria %A van der Lee, Sven J %A Amlie-Wolf, Alexandre %A Bellenguez, Céline %A Frizatti, Aura %A Chouraki, Vincent %A Martin, Eden R %A Sleegers, Kristel %A Badarinarayan, Nandini %A Jakobsdottir, Johanna %A Hamilton-Nelson, Kara L %A Moreno-Grau, Sonia %A Olaso, Robert %A Raybould, Rachel %A Chen, Yuning %A Kuzma, Amanda B %A Hiltunen, Mikko %A Morgan, Taniesha %A Ahmad, Shahzad %A Vardarajan, Badri N %A Epelbaum, Jacques %A Hoffmann, Per %A Boada, Mercè %A Beecham, Gary W %A Garnier, Jean-Guillaume %A Harold, Denise %A Fitzpatrick, Annette L %A Valladares, Otto %A Moutet, Marie-Laure %A Gerrish, Amy %A Smith, Albert V %A Qu, Liming %A Bacq, Delphine %A Denning, Nicola %A Jian, Xueqiu %A Zhao, Yi %A Del Zompo, Maria %A Fox, Nick C %A Choi, Seung-Hoan %A Mateo, Ignacio %A Hughes, Joseph T %A Adams, Hieab H %A Malamon, John %A Sanchez-Garcia, Florentino %A Patel, Yogen %A Brody, Jennifer A %A Dombroski, Beth A %A Naranjo, Maria Candida Deniz %A Daniilidou, Makrina %A Eiriksdottir, Gudny %A Mukherjee, Shubhabrata %A Wallon, David %A Uphill, James %A Aspelund, Thor %A Cantwell, Laura B %A Garzia, Fabienne %A Galimberti, Daniela %A Hofer, Edith %A Butkiewicz, Mariusz %A Fin, Bertrand %A Scarpini, Elio %A Sarnowski, Chloe %A Bush, Will S %A Meslage, Stéphane %A Kornhuber, Johannes %A White, Charles C %A Song, Yuenjoo %A Barber, Robert C %A Engelborghs, Sebastiaan %A Sordon, Sabrina %A Voijnovic, Dina %A Adams, Perrie M %A Vandenberghe, Rik %A Mayhaus, Manuel %A Cupples, L Adrienne %A Albert, Marilyn S %A De Deyn, Peter P %A Gu, Wei %A Himali, Jayanadra J %A Beekly, Duane %A Squassina, Alessio %A Hartmann, Annette M %A Orellana, Adelina %A Blacker, Deborah %A Rodriguez-Rodriguez, Eloy %A Lovestone, Simon %A Garcia, Melissa E %A Doody, Rachelle S %A Munoz-Fernadez, Carmen %A Sussams, Rebecca %A Lin, Honghuang %A Fairchild, Thomas J %A Benito, Yolanda A %A Holmes, Clive %A Karamujić-Čomić, Hata %A Frosch, Matthew P %A Thonberg, Hakan %A Maier, Wolfgang %A Roshchupkin, Gennady %A Ghetti, Bernardino %A Giedraitis, Vilmantas %A Kawalia, Amit %A Li, Shuo %A Huebinger, Ryan M %A Kilander, Lena %A Moebus, Susanne %A Hernández, Isabel %A Kamboh, M Ilyas %A Brundin, RoseMarie %A Turton, James %A Yang, Qiong %A Katz, Mindy J %A Concari, Letizia %A Lord, Jenny %A Beiser, Alexa S %A Keene, C Dirk %A Helisalmi, Seppo %A Kloszewska, Iwona %A Kukull, Walter A %A Koivisto, Anne Maria %A Lynch, Aoibhinn %A Tarraga, Lluis %A Larson, Eric B %A Haapasalo, Annakaisa %A Lawlor, Brian %A Mosley, Thomas H %A Lipton, Richard B %A Solfrizzi, Vincenzo %A Gill, Michael %A Longstreth, W T %A Montine, Thomas J %A Frisardi, Vincenza %A Diez-Fairen, Monica %A Rivadeneira, Fernando %A Petersen, Ronald C %A Deramecourt, Vincent %A Alvarez, Ignacio %A Salani, Francesca %A Ciaramella, Antonio %A Eric Boerwinkle %A Reiman, Eric M %A Fiévet, Nathalie %A Rotter, Jerome I %A Reisch, Joan S %A Hanon, Olivier %A Cupidi, Chiara %A Andre Uitterlinden, A G %A Royall, Donald R %A Dufouil, Carole %A Maletta, Raffaele Giovanni %A de Rojas, Itziar %A Sano, Mary %A Brice, Alexis %A Cecchetti, Roberta %A George-Hyslop, Peter St %A Ritchie, Karen %A Tsolaki, Magda %A Tsuang, Debby W %A Dubois, Bruno %A Craig, David %A Wu, Chuang-Kuo %A Soininen, Hilkka %A Avramidou, Despoina %A Albin, Roger L %A Fratiglioni, Laura %A Germanou, Antonia %A Apostolova, Liana G %A Keller, Lina %A Koutroumani, Maria %A Arnold, Steven E %A Panza, Francesco %A Gkatzima, Olymbia %A Asthana, Sanjay %A Hannequin, Didier %A Whitehead, Patrice %A Atwood, Craig S %A Caffarra, Paolo %A Hampel, Harald %A Quintela, Inés %A Carracedo, Ángel %A Lannfelt, Lars %A Rubinsztein, David C %A Barnes, Lisa L %A Pasquier, Florence %A Frölich, Lutz %A Barral, Sandra %A McGuinness, Bernadette %A Beach, Thomas G %A Johnston, Janet A %A Becker, James T %A Passmore, Peter %A Bigio, Eileen H %A Schott, Jonathan M %A Bird, Thomas D %A Warren, Jason D %A Boeve, Bradley F %A Lupton, Michelle K %A Bowen, James D %A Proitsi, Petra %A Boxer, Adam %A Powell, John F %A Burke, James R %A Kauwe, John S K %A Burns, Jeffrey M %A Mancuso, Michelangelo %A Buxbaum, Joseph D %A Bonuccelli, Ubaldo %A Cairns, Nigel J %A McQuillin, Andrew %A Cao, Chuanhai %A Livingston, Gill %A Carlson, Chris S %A Bass, Nicholas J %A Carlsson, Cynthia M %A Hardy, John %A Carney, Regina M %A Bras, Jose %A Carrasquillo, Minerva M %A Guerreiro, Rita %A Allen, Mariet %A Chui, Helena C %A Fisher, Elizabeth %A Masullo, Carlo %A Crocco, Elizabeth A %A DeCarli, Charles %A Bisceglio, Gina %A Dick, Malcolm %A Ma, Li %A Duara, Ranjan %A Graff-Radford, Neill R %A Evans, Denis A %A Hodges, Angela %A Faber, Kelley M %A Scherer, Martin %A Fallon, Kenneth B %A Riemenschneider, Matthias %A Fardo, David W %A Heun, Reinhard %A Farlow, Martin R %A Kölsch, Heike %A Ferris, Steven %A Leber, Markus %A Foroud, Tatiana M %A Heuser, Isabella %A Galasko, Douglas R %A Giegling, Ina %A Gearing, Marla %A Hüll, Michael %A Geschwind, Daniel H %A Gilbert, John R %A Morris, John %A Green, Robert C %A Mayo, Kevin %A Growdon, John H %A Feulner, Thomas %A Hamilton, Ronald L %A Harrell, Lindy E %A Drichel, Dmitriy %A Honig, Lawrence S %A Cushion, Thomas D %A Huentelman, Matthew J %A Hollingworth, Paul %A Hulette, Christine M %A Hyman, Bradley T %A Marshall, Rachel %A Jarvik, Gail P %A Meggy, Alun %A Abner, Erin %A Menzies, Georgina E %A Jin, Lee-Way %A Leonenko, Ganna %A Real, Luis M %A Jun, Gyungah R %A Baldwin, Clinton T %A Grozeva, Detelina %A Karydas, Anna %A Russo, Giancarlo %A Kaye, Jeffrey A %A Kim, Ronald %A Jessen, Frank %A Kowall, Neil W %A Vellas, Bruno %A Kramer, Joel H %A Vardy, Emma %A LaFerla, Frank M %A Jöckel, Karl-Heinz %A Lah, James J %A Dichgans, Martin %A Leverenz, James B %A Mann, David %A Levey, Allan I %A Pickering-Brown, Stuart %A Lieberman, Andrew P %A Klopp, Norman %A Lunetta, Kathryn L %A Wichmann, H-Erich %A Lyketsos, Constantine G %A Morgan, Kevin %A Marson, Daniel C %A Brown, Kristelle %A Martiniuk, Frank %A Medway, Christopher %A Mash, Deborah C %A Nöthen, Markus M %A Masliah, Eliezer %A Hooper, Nigel M %A McCormick, Wayne C %A Daniele, Antonio %A McCurry, Susan M %A Bayer, Anthony %A McDavid, Andrew N %A Gallacher, John %A McKee, Ann C %A van den Bussche, Hendrik %A Mesulam, Marsel %A Brayne, Carol %A Miller, Bruce L %A Riedel-Heller, Steffi %A Miller, Carol A %A Miller, Joshua W %A Al-Chalabi, Ammar %A Morris, John C %A Shaw, Christopher E %A Myers, Amanda J %A Wiltfang, Jens %A O'Bryant, Sid %A Olichney, John M %A Alvarez, Victoria %A Parisi, Joseph E %A Singleton, Andrew B %A Paulson, Henry L %A Collinge, John %A Perry, William R %A Mead, Simon %A Peskind, Elaine %A Cribbs, David H %A Rossor, Martin %A Pierce, Aimee %A Ryan, Natalie S %A Poon, Wayne W %A Nacmias, Benedetta %A Potter, Huntington %A Sorbi, Sandro %A Quinn, Joseph F %A Sacchinelli, Eleonora %A Raj, Ashok %A Spalletta, Gianfranco %A Raskind, Murray %A Caltagirone, Carlo %A Bossù, Paola %A Orfei, Maria Donata %A Reisberg, Barry %A Clarke, Robert %A Reitz, Christiane %A Smith, A David %A Ringman, John M %A Warden, Donald %A Roberson, Erik D %A Wilcock, Gordon %A Rogaeva, Ekaterina %A Bruni, Amalia Cecilia %A Rosen, Howard J %A Gallo, Maura %A Rosenberg, Roger N %A Ben-Shlomo, Yoav %A Sager, Mark A %A Mecocci, Patrizia %A Saykin, Andrew J %A Pastor, Pau %A Cuccaro, Michael L %A Vance, Jeffery M %A Schneider, Julie A %A Schneider, Lori S %A Slifer, Susan %A Seeley, William W %A Smith, Amanda G %A Sonnen, Joshua A %A Spina, Salvatore %A Stern, Robert A %A Swerdlow, Russell H %A Tang, Mitchell %A Tanzi, Rudolph E %A Trojanowski, John Q %A Troncoso, Juan C %A Van Deerlin, Vivianna M %A Van Eldik, Linda J %A Vinters, Harry V %A Vonsattel, Jean Paul %A Weintraub, Sandra %A Welsh-Bohmer, Kathleen A %A Wilhelmsen, Kirk C %A Williamson, Jennifer %A Wingo, Thomas S %A Woltjer, Randall L %A Wright, Clinton B %A Yu, Chang-En %A Yu, Lei %A Saba, Yasaman %A Pilotto, Alberto %A Bullido, María J %A Peters, Oliver %A Crane, Paul K %A Bennett, David %A Bosco, Paola %A Coto, Eliecer %A Boccardi, Virginia %A De Jager, Phil L %A Lleo, Alberto %A Warner, Nick %A Lopez, Oscar L %A Ingelsson, Martin %A Deloukas, Panagiotis %A Cruchaga, Carlos %A Graff, Caroline %A Gwilliam, Rhian %A Fornage, Myriam %A Goate, Alison M %A Sánchez-Juan, Pascual %A Kehoe, Patrick G %A Amin, Najaf %A Ertekin-Taner, Nilifur %A Berr, Claudine %A Debette, Stephanie %A Love, Seth %A Launer, Lenore J %A Younkin, Steven G %A Dartigues, Jean-François %A Corcoran, Chris %A Ikram, M Arfan %A Dickson, Dennis W %A Nicolas, Gaël %A Campion, Dominique %A Tschanz, JoAnn %A Schmidt, Helena %A Hakonarson, Hakon %A Clarimon, Jordi %A Munger, Ron %A Schmidt, Reinhold %A Farrer, Lindsay A %A Van Broeckhoven, Christine %A C O'Donovan, Michael %A DeStefano, Anita L %A Jones, Lesley %A Haines, Jonathan L %A Deleuze, Jean-François %A Owen, Michael J %A Gudnason, Vilmundur %A Mayeux, Richard %A Escott-Price, Valentina %A Psaty, Bruce M %A Ramirez, Alfredo %A Wang, Li-San %A Ruiz, Agustin %A van Duijn, Cornelia M %A Holmans, Peter A %A Seshadri, Sudha %A Williams, Julie %A Amouyel, Phillippe %A Schellenberg, Gerard D %A Lambert, Jean-Charles %A Pericak-Vance, Margaret A %K Aged %K Alzheimer Disease %K Amyloid beta-Peptides %K Case-Control Studies %K Female %K Genetic Loci %K Genetic Predisposition to Disease %K Genetic Testing %K Genome-Wide Association Study %K Haplotypes %K Humans %K Immunity %K Lipid Metabolism %K Lipids %K Male %K tau Proteins %X

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), 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.

%B Nat Genet %V 51 %P 414-430 %8 2019 Mar %G eng %N 3 %1 https://www.ncbi.nlm.nih.gov/pubmed/30820047?dopt=Abstract %R 10.1038/s41588-019-0358-2 %0 Journal Article %J Nat Genet %D 2017 %T Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. %A Sims, Rebecca %A van der Lee, Sven J %A Naj, Adam C %A Bellenguez, Céline %A Badarinarayan, Nandini %A Jakobsdottir, Johanna %A Kunkle, Brian W %A Boland, Anne %A Raybould, Rachel %A Bis, Joshua C %A Martin, Eden R %A Grenier-Boley, Benjamin %A Heilmann-Heimbach, Stefanie %A Chouraki, Vincent %A Kuzma, Amanda B %A Sleegers, Kristel %A Vronskaya, Maria %A Ruiz, Agustin %A Graham, Robert R %A Olaso, Robert %A Hoffmann, Per %A Grove, Megan L %A Vardarajan, Badri N %A Hiltunen, Mikko %A Nöthen, Markus M %A White, Charles C %A Hamilton-Nelson, Kara L %A Epelbaum, Jacques %A Maier, Wolfgang %A Choi, Seung-Hoan %A Beecham, Gary W %A Dulary, Cécile %A Herms, Stefan %A Smith, Albert V %A Funk, Cory C %A Derbois, Céline %A Forstner, Andreas J %A Ahmad, Shahzad %A Li, Hongdong %A Bacq, Delphine %A Harold, Denise %A Satizabal, Claudia L %A Valladares, Otto %A Squassina, Alessio %A Thomas, Rhodri %A Brody, Jennifer A %A Qu, Liming %A Sánchez-Juan, Pascual %A Morgan, Taniesha %A Wolters, Frank J %A Zhao, Yi %A Garcia, Florentino Sanchez %A Denning, Nicola %A Fornage, Myriam %A Malamon, John %A Naranjo, Maria Candida Deniz %A Majounie, Elisa %A Mosley, Thomas H %A Dombroski, Beth %A Wallon, David %A Lupton, Michelle K %A Dupuis, Josée %A Whitehead, Patrice %A Fratiglioni, Laura %A Medway, Christopher %A Jian, Xueqiu %A Mukherjee, Shubhabrata %A Keller, Lina %A Brown, Kristelle %A Lin, Honghuang %A Cantwell, Laura B %A Panza, Francesco %A McGuinness, Bernadette %A Moreno-Grau, Sonia %A Burgess, Jeremy D %A Solfrizzi, Vincenzo %A Proitsi, Petra %A Adams, Hieab H %A Allen, Mariet %A Seripa, Davide %A Pastor, Pau %A Cupples, L Adrienne %A Price, Nathan D %A Hannequin, Didier %A Frank-García, Ana %A Levy, Daniel %A Chakrabarty, Paramita %A Caffarra, Paolo %A Giegling, Ina %A Beiser, Alexa S %A Giedraitis, Vilmantas %A Hampel, Harald %A Garcia, Melissa E %A Wang, Xue %A Lannfelt, Lars %A Mecocci, Patrizia %A Eiriksdottir, Gudny %A Crane, Paul K %A Pasquier, Florence %A Boccardi, Virginia %A Henández, Isabel %A Barber, Robert C %A Scherer, Martin %A Tarraga, Lluis %A Adams, Perrie M %A Leber, Markus %A Chen, Yuning %A Albert, Marilyn S %A Riedel-Heller, Steffi %A Emilsson, Valur %A Beekly, Duane %A Braae, Anne %A Schmidt, Reinhold %A Blacker, Deborah %A Masullo, Carlo %A Schmidt, Helena %A Doody, Rachelle S %A Spalletta, Gianfranco %A Longstreth, W T %A Fairchild, Thomas J %A Bossù, Paola %A Lopez, Oscar L %A Frosch, Matthew P %A Sacchinelli, Eleonora %A Ghetti, Bernardino %A Yang, Qiong %A Huebinger, Ryan M %A Jessen, Frank %A Li, Shuo %A Kamboh, M Ilyas %A Morris, John %A Sotolongo-Grau, Oscar %A Katz, Mindy J %A Corcoran, Chris %A Dunstan, Melanie %A Braddel, Amy %A Thomas, Charlene %A Meggy, Alun %A Marshall, Rachel %A Gerrish, Amy %A Chapman, Jade %A Aguilar, Miquel %A Taylor, Sarah %A Hill, Matt %A Fairén, Mònica Díez %A Hodges, Angela %A Vellas, Bruno %A Soininen, Hilkka %A Kloszewska, Iwona %A Daniilidou, Makrina %A Uphill, James %A Patel, Yogen %A Hughes, Joseph T %A Lord, Jenny %A Turton, James %A Hartmann, Annette M %A Cecchetti, Roberta %A Fenoglio, Chiara %A Serpente, Maria %A Arcaro, Marina %A Caltagirone, Carlo %A Orfei, Maria Donata %A Ciaramella, Antonio %A Pichler, Sabrina %A Mayhaus, Manuel %A Gu, Wei %A Lleo, Alberto %A Fortea, Juan %A Blesa, Rafael %A Barber, Imelda S %A Brookes, Keeley %A Cupidi, Chiara %A Maletta, Raffaele Giovanni %A Carrell, David %A Sorbi, Sandro %A Moebus, Susanne %A Urbano, Maria %A Pilotto, Alberto %A Kornhuber, Johannes %A Bosco, Paolo %A Todd, Stephen %A Craig, David %A Johnston, Janet %A Gill, Michael %A Lawlor, Brian %A Lynch, Aoibhinn %A Fox, Nick C %A Hardy, John %A Albin, Roger L %A Apostolova, Liana G %A Arnold, Steven E %A Asthana, Sanjay %A Atwood, Craig S %A Baldwin, Clinton T %A Barnes, Lisa L %A Barral, Sandra %A Beach, Thomas G %A Becker, James T %A Bigio, Eileen H %A Bird, Thomas D %A Boeve, Bradley F %A Bowen, James D %A Boxer, Adam %A Burke, James R %A Burns, Jeffrey M %A Buxbaum, Joseph D %A Cairns, Nigel J %A Cao, Chuanhai %A Carlson, Chris S %A Carlsson, Cynthia M %A Carney, Regina M %A Carrasquillo, Minerva M %A Carroll, Steven L %A Diaz, Carolina Ceballos %A Chui, Helena C %A Clark, David G %A Cribbs, David H %A Crocco, Elizabeth A %A DeCarli, Charles %A Dick, Malcolm %A Duara, Ranjan %A Evans, Denis A %A Faber, Kelley M %A Fallon, Kenneth B %A Fardo, David W %A Farlow, Martin R %A Ferris, Steven %A Foroud, Tatiana M %A Galasko, Douglas R %A Gearing, Marla %A Geschwind, Daniel H %A Gilbert, John R %A Graff-Radford, Neill R %A Green, Robert C %A Growdon, John H %A Hamilton, Ronald L %A Harrell, Lindy E %A Honig, Lawrence S %A Huentelman, Matthew J %A Hulette, Christine M %A Hyman, Bradley T %A Jarvik, Gail P %A Abner, Erin %A Jin, Lee-Way %A Jun, Gyungah %A Karydas, Anna %A Kaye, Jeffrey A %A Kim, Ronald %A Kowall, Neil W %A Kramer, Joel H %A LaFerla, Frank M %A Lah, James J %A Leverenz, James B %A Levey, Allan I %A Li, Ge %A Lieberman, Andrew P %A Lunetta, Kathryn L %A Lyketsos, Constantine G %A Marson, Daniel C %A Martiniuk, Frank %A Mash, Deborah C %A Masliah, Eliezer %A McCormick, Wayne C %A McCurry, Susan M %A McDavid, Andrew N %A McKee, Ann C %A Mesulam, Marsel %A Miller, Bruce L %A Miller, Carol A %A Miller, Joshua W %A Morris, John C %A Murrell, Jill R %A Myers, Amanda J %A O'Bryant, Sid %A Olichney, John M %A Pankratz, Vernon S %A Parisi, Joseph E %A Paulson, Henry L %A Perry, William %A Peskind, Elaine %A Pierce, Aimee %A Poon, Wayne W %A Potter, Huntington %A Quinn, Joseph F %A Raj, Ashok %A Raskind, Murray %A Reisberg, Barry %A Reitz, Christiane %A Ringman, John M %A Roberson, Erik D %A Rogaeva, Ekaterina %A Rosen, Howard J %A Rosenberg, Roger N %A Sager, Mark A %A Saykin, Andrew J %A Schneider, Julie A %A Schneider, Lon S %A Seeley, William W %A Smith, Amanda G %A Sonnen, Joshua A %A Spina, Salvatore %A Stern, Robert A %A Swerdlow, Russell H %A Tanzi, Rudolph E %A Thornton-Wells, Tricia A %A Trojanowski, John Q %A Troncoso, Juan C %A Van Deerlin, Vivianna M %A Van Eldik, Linda J %A Vinters, Harry V %A Vonsattel, Jean Paul %A Weintraub, Sandra %A Welsh-Bohmer, Kathleen A %A Wilhelmsen, Kirk C %A Williamson, Jennifer %A Wingo, Thomas S %A Woltjer, Randall L %A Wright, Clinton B %A Yu, Chang-En %A Yu, Lei %A Garzia, Fabienne %A Golamaully, Feroze %A Septier, Gislain %A Engelborghs, Sebastien %A Vandenberghe, Rik %A De Deyn, Peter P %A Fernadez, Carmen Muñoz %A Benito, Yoland Aladro %A Thonberg, Hakan %A Forsell, Charlotte %A Lilius, Lena %A Kinhult-Stählbom, Anne %A Kilander, Lena %A Brundin, RoseMarie %A Concari, Letizia %A Helisalmi, Seppo %A Koivisto, Anne Maria %A Haapasalo, Annakaisa %A Dermecourt, Vincent %A Fiévet, Nathalie %A Hanon, Olivier %A Dufouil, Carole %A Brice, Alexis %A Ritchie, Karen %A Dubois, Bruno %A Himali, Jayanadra J %A Keene, C Dirk %A Tschanz, JoAnn %A Fitzpatrick, Annette L %A Kukull, Walter A %A Norton, Maria %A Aspelund, Thor %A Larson, Eric B %A Munger, Ron %A Rotter, Jerome I %A Lipton, Richard B %A Bullido, María J %A Hofman, Albert %A Montine, Thomas J %A Coto, Eliecer %A Eric Boerwinkle %A Petersen, Ronald C %A Alvarez, Victoria %A Rivadeneira, Fernando %A Reiman, Eric M %A Gallo, Maura %A O'Donnell, Christopher J %A Reisch, Joan S %A Bruni, Amalia Cecilia %A Royall, Donald R %A Dichgans, Martin %A Sano, Mary %A Galimberti, Daniela %A St George-Hyslop, Peter %A Scarpini, Elio %A Tsuang, Debby W %A Mancuso, Michelangelo %A Bonuccelli, Ubaldo %A Winslow, Ashley R %A Daniele, Antonio %A Wu, Chuang-Kuo %A Peters, Oliver %A Nacmias, Benedetta %A Riemenschneider, Matthias %A Heun, Reinhard %A Brayne, Carol %A Rubinsztein, David C %A Bras, Jose %A Guerreiro, Rita %A Al-Chalabi, Ammar %A Shaw, Christopher E %A Collinge, John %A Mann, David %A Tsolaki, Magda %A Clarimon, Jordi %A Sussams, Rebecca %A Lovestone, Simon %A O'Donovan, Michael C %A Owen, Michael J %A Behrens, Timothy W %A Mead, Simon %A Goate, Alison M %A Uitterlinden, André G %A Holmes, Clive %A Cruchaga, Carlos %A Ingelsson, Martin %A Bennett, David A %A Powell, John %A Golde, Todd E %A Graff, Caroline %A De Jager, Philip L %A Morgan, Kevin %A Ertekin-Taner, Nilufer %A Combarros, Onofre %A Psaty, Bruce M %A Passmore, Peter %A Younkin, Steven G %A Berr, Claudine %A Gudnason, Vilmundur %A Rujescu, Dan %A Dickson, Dennis W %A Dartigues, Jean-François %A DeStefano, Anita L %A Ortega-Cubero, Sara %A Hakonarson, Hakon %A Campion, Dominique %A Boada, Mercè %A Kauwe, John Keoni %A Farrer, Lindsay A %A Van Broeckhoven, Christine %A Ikram, M Arfan %A Jones, Lesley %A Haines, Jonathan L %A Tzourio, Christophe %A Launer, Lenore J %A Escott-Price, Valentina %A Mayeux, Richard %A Deleuze, Jean-François %A Amin, Najaf %A Holmans, Peter A %A Pericak-Vance, Margaret A %A Amouyel, Philippe %A van Duijn, Cornelia M %A Ramirez, Alfredo %A Wang, Li-San %A Lambert, Jean-Charles %A Seshadri, Sudha %A Williams, Julie %A Schellenberg, Gerard D %K Adaptor Proteins, Signal Transducing %K Alzheimer Disease %K Amino Acid Sequence %K Case-Control Studies %K Exome %K Gene Expression Profiling %K Gene Frequency %K Genetic Predisposition to Disease %K Genotype %K Humans %K Immunity, Innate %K Linkage Disequilibrium %K Membrane Glycoproteins %K Microglia %K Odds Ratio %K Phospholipase C gamma %K Polymorphism, Single Nucleotide %K Protein Interaction Maps %K Receptors, Immunologic %K Sequence Homology, Amino Acid %X

We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10, odds ratio (OR) = 0.68, minor allele frequency (MAF) = 0.0059, MAF = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10, OR = 1.43, MAF = 0.011, MAF = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10, OR = 1.67, MAF = 0.0143, MAF = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

%B Nat Genet %V 49 %P 1373-1384 %8 2017 Sep %G eng %N 9 %1 https://www.ncbi.nlm.nih.gov/pubmed/28714976?dopt=Abstract %R 10.1038/ng.3916 %0 Journal Article %J PLoS One %D 2014 %T Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. %A Escott-Price, Valentina %A Bellenguez, Céline %A Wang, Li-San %A Choi, Seung-Hoan %A Harold, Denise %A Jones, Lesley %A Holmans, Peter %A Gerrish, Amy %A Vedernikov, Alexey %A Richards, Alexander %A DeStefano, Anita L %A Lambert, Jean-Charles %A Ibrahim-Verbaas, Carla A %A Naj, Adam C %A Sims, Rebecca %A Jun, Gyungah %A Bis, Joshua C %A Beecham, Gary W %A Grenier-Boley, Benjamin %A Russo, Giancarlo %A Thornton-Wells, Tricia A %A Denning, Nicola %A Smith, Albert V %A Chouraki, Vincent %A Thomas, Charlene %A Ikram, M Arfan %A Zelenika, Diana %A Vardarajan, Badri N %A Kamatani, Yoichiro %A Lin, Chiao-Feng %A Schmidt, Helena %A Kunkle, Brian %A Dunstan, Melanie L %A Vronskaya, Maria %A Johnson, Andrew D %A Ruiz, Agustin %A Bihoreau, Marie-Therese %A Reitz, Christiane %A Pasquier, Florence %A Hollingworth, Paul %A Hanon, Olivier %A Fitzpatrick, Annette L %A Buxbaum, Joseph D %A Campion, Dominique %A Crane, Paul K %A Baldwin, Clinton %A Becker, Tim %A Gudnason, Vilmundur %A Cruchaga, Carlos %A Craig, David %A Amin, Najaf %A Berr, Claudine %A Lopez, Oscar L %A De Jager, Philip L %A Deramecourt, Vincent %A Johnston, Janet A %A Evans, Denis %A Lovestone, Simon %A Letenneur, Luc %A Hernández, Isabel %A Rubinsztein, David C %A Eiriksdottir, Gudny %A Sleegers, Kristel %A Goate, Alison M %A Fiévet, Nathalie %A Huentelman, Matthew J %A Gill, Michael %A Brown, Kristelle %A Kamboh, M Ilyas %A Keller, Lina %A Barberger-Gateau, Pascale %A McGuinness, Bernadette %A Larson, Eric B %A Myers, Amanda J %A Dufouil, Carole %A Todd, Stephen %A Wallon, David %A Love, Seth %A Rogaeva, Ekaterina %A Gallacher, John %A George-Hyslop, Peter St %A Clarimon, Jordi %A Lleo, Alberto %A Bayer, Anthony %A Tsuang, Debby W %A Yu, Lei %A Tsolaki, Magda %A Bossù, Paola %A Spalletta, Gianfranco %A Proitsi, Petra %A Collinge, John %A Sorbi, Sandro %A Garcia, Florentino Sanchez %A Fox, Nick C %A Hardy, John %A Naranjo, Maria Candida Deniz %A Bosco, Paolo %A Clarke, Robert %A Brayne, Carol %A Galimberti, Daniela %A Scarpini, Elio %A Bonuccelli, Ubaldo %A Mancuso, Michelangelo %A Siciliano, Gabriele %A Moebus, Susanne %A Mecocci, Patrizia %A Zompo, Maria Del %A Maier, Wolfgang %A Hampel, Harald %A Pilotto, Alberto %A Frank-García, Ana %A Panza, Francesco %A Solfrizzi, Vincenzo %A Caffarra, Paolo %A Nacmias, Benedetta %A Perry, William %A Mayhaus, Manuel %A Lannfelt, Lars %A Hakonarson, Hakon %A Pichler, Sabrina %A Carrasquillo, Minerva M %A Ingelsson, Martin %A Beekly, Duane %A Alvarez, Victoria %A Zou, Fanggeng %A Valladares, Otto %A Younkin, Steven G %A Coto, Eliecer %A Hamilton-Nelson, Kara L %A Gu, Wei %A Razquin, Cristina %A Pastor, Pau %A Mateo, Ignacio %A Owen, Michael J %A Faber, Kelley M %A Jonsson, Palmi V %A Combarros, Onofre %A O'Donovan, Michael C %A Cantwell, Laura B %A Soininen, Hilkka %A Blacker, Deborah %A Mead, Simon %A Mosley, Thomas H %A Bennett, David A %A Harris, Tamara B %A Fratiglioni, Laura %A Holmes, Clive %A de Bruijn, Renee F A G %A Passmore, Peter %A Montine, Thomas J %A Bettens, Karolien %A Rotter, Jerome I %A Brice, Alexis %A Morgan, Kevin %A Foroud, Tatiana M %A Kukull, Walter A %A Hannequin, Didier %A Powell, John F %A Nalls, Michael A %A Ritchie, Karen %A Lunetta, Kathryn L %A Kauwe, John S K %A Eric Boerwinkle %A Riemenschneider, Matthias %A Boada, Mercè %A Hiltunen, Mikko %A Martin, Eden R %A Schmidt, Reinhold %A Rujescu, Dan %A Dartigues, Jean-François %A Mayeux, Richard %A Tzourio, Christophe %A Hofman, Albert %A Nöthen, Markus M %A Graff, Caroline %A Psaty, Bruce M %A Haines, Jonathan L %A Lathrop, Mark %A Pericak-Vance, Margaret A %A Launer, Lenore J %A Van Broeckhoven, Christine %A Farrer, Lindsay A %A van Duijn, Cornelia M %A Ramirez, Alfredo %A Seshadri, Sudha %A Schellenberg, Gerard D %A Amouyel, Philippe %A Williams, Julie %K Alzheimer Disease %K Carrier Proteins %K Case-Control Studies %K Genome-Wide Association Study %K Heat-Shock Proteins %K Humans %K Polymorphism, Single Nucleotide %K Receptors, Antigen, B-Cell %X

BACKGROUND: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.

PRINCIPAL FINDINGS: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6) and 14 (IGHV1-67 p = 7.9×10-8) which indexed novel susceptibility loci.

SIGNIFICANCE: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

%B PLoS One %V 9 %P e94661 %8 2014 %G eng %N 6 %1 https://www.ncbi.nlm.nih.gov/pubmed/24922517?dopt=Abstract %R 10.1371/journal.pone.0094661