%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 Genet %D 2022 %T New insights into the genetic etiology of Alzheimer's disease and related dementias. %A Bellenguez, Céline %A Küçükali, Fahri %A Jansen, Iris E %A Kleineidam, Luca %A Moreno-Grau, Sonia %A Amin, Najaf %A Naj, Adam C %A Campos-Martin, Rafael %A Grenier-Boley, Benjamin %A Andrade, Victor %A Holmans, Peter A %A Boland, Anne %A Damotte, Vincent %A van der Lee, Sven J %A Costa, Marcos R %A Kuulasmaa, Teemu %A Yang, Qiong %A de Rojas, Itziar %A Bis, Joshua C %A Yaqub, Amber %A Prokic, Ivana %A Chapuis, Julien %A Ahmad, Shahzad %A Giedraitis, Vilmantas %A Aarsland, Dag %A García-González, Pablo %A Abdelnour, Carla %A Alarcón-Martín, Emilio %A Alcolea, Daniel %A Alegret, Montserrat %A Alvarez, Ignacio %A Alvarez, Victoria %A Armstrong, Nicola J %A Tsolaki, Anthoula %A Antúnez, Carmen %A Appollonio, Ildebrando %A Arcaro, Marina %A Archetti, Silvana %A Pastor, Alfonso Arias %A Arosio, Beatrice %A Athanasiu, Lavinia %A Bailly, Henri %A Banaj, Nerisa %A Baquero, Miquel %A Barral, Sandra %A Beiser, Alexa %A Pastor, Ana Belén %A Below, Jennifer E %A Benchek, Penelope %A Benussi, Luisa %A Berr, Claudine %A Besse, Céline %A Bessi, Valentina %A Binetti, Giuliano %A Bizarro, Alessandra %A Blesa, Rafael %A Boada, Mercè %A Eric Boerwinkle %A Borroni, Barbara %A Boschi, Silvia %A Bossù, Paola %A Bråthen, Geir %A Bressler, Jan %A Bresner, Catherine %A Brodaty, Henry %A Brookes, Keeley J %A Brusco, Luis Ignacio %A Buiza-Rueda, Dolores %A Bûrger, Katharina %A Burholt, Vanessa %A Bush, William S %A Calero, Miguel %A Cantwell, Laura B %A Chêne, Geneviève %A Chung, Jaeyoon %A Cuccaro, Michael L %A Carracedo, Ángel %A Cecchetti, Roberta %A Cervera-Carles, Laura %A Charbonnier, Camille %A Chen, Hung-Hsin %A Chillotti, Caterina %A Ciccone, Simona %A Claassen, Jurgen A H R %A Clark, Christopher %A Conti, Elisa %A Corma-Gómez, Anaïs %A Costantini, Emanuele %A Custodero, Carlo %A Daian, Delphine %A Dalmasso, Maria Carolina %A Daniele, Antonio %A Dardiotis, Efthimios %A Dartigues, Jean-François %A de Deyn, Peter Paul %A de Paiva Lopes, Katia %A de Witte, Lot D %A Debette, Stephanie %A Deckert, Jürgen %A Del Ser, Teodoro %A Denning, Nicola %A DeStefano, Anita %A Dichgans, Martin %A Diehl-Schmid, Janine %A Diez-Fairen, Monica %A Rossi, Paolo Dionigi %A Djurovic, Srdjan %A Duron, Emmanuelle %A Düzel, Emrah %A Dufouil, Carole %A Eiriksdottir, Gudny %A Engelborghs, Sebastiaan %A Escott-Price, Valentina %A Espinosa, Ana %A Ewers, Michael %A Faber, Kelley M %A Fabrizio, Tagliavini %A Nielsen, Sune Fallgaard %A Fardo, David W %A Farotti, Lucia %A Fenoglio, Chiara %A Fernández-Fuertes, Marta %A Ferrari, Raffaele %A Ferreira, Catarina B %A Ferri, Evelyn %A Fin, Bertrand %A Fischer, Peter %A Fladby, Tormod %A Fließbach, Klaus %A Fongang, Bernard %A Fornage, Myriam %A Fortea, Juan %A Foroud, Tatiana M %A Fostinelli, Silvia %A Fox, Nick C %A Franco-Macías, Emlio %A Bullido, María J %A Frank-García, Ana %A Froelich, Lutz %A Fulton-Howard, Brian %A Galimberti, Daniela %A García-Alberca, Jose María %A García-González, Pablo %A García-Madrona, Sebastián %A Garcia-Ribas, Guillermo %A Ghidoni, Roberta %A Giegling, Ina %A Giorgio, Giaccone %A Goate, Alison M %A Goldhardt, Oliver %A Gomez-Fonseca, Duber %A González-Perez, Antonio %A Graff, Caroline %A Grande, Giulia %A Green, Emma %A Grimmer, Timo %A Grünblatt, Edna %A Grunin, Michelle %A Gudnason, Vilmundur %A Guetta-Baranes, Tamar %A Haapasalo, Annakaisa %A Hadjigeorgiou, Georgios %A Haines, Jonathan L %A Hamilton-Nelson, Kara L %A Hampel, Harald %A Hanon, Olivier %A Hardy, John %A Hartmann, Annette M %A Hausner, Lucrezia %A Harwood, Janet %A Heilmann-Heimbach, Stefanie %A Helisalmi, Seppo %A Heneka, Michael T %A Hernández, Isabel %A Herrmann, Martin J %A Hoffmann, Per %A Holmes, Clive %A Holstege, Henne %A Vilas, Raquel Huerto %A Hulsman, Marc %A Humphrey, Jack %A Biessels, Geert Jan %A Jian, Xueqiu %A Johansson, Charlotte %A Jun, Gyungah R %A Kastumata, Yuriko %A Kauwe, John %A Kehoe, Patrick G %A Kilander, Lena %A Ståhlbom, Anne Kinhult %A Kivipelto, Miia %A Koivisto, Anne %A Kornhuber, Johannes %A Kosmidis, Mary H %A Kukull, Walter A %A Kuksa, Pavel P %A Kunkle, Brian W %A Kuzma, Amanda B %A Lage, Carmen %A Laukka, Erika J %A Launer, Lenore %A Lauria, Alessandra %A Lee, Chien-Yueh %A Lehtisalo, Jenni %A Lerch, Ondrej %A Lleo, Alberto %A Longstreth, William %A Lopez, Oscar %A de Munain, Adolfo Lopez %A Love, Seth %A Löwemark, Malin %A Luckcuck, Lauren %A Lunetta, Kathryn L %A Ma, Yiyi %A Macías, Juan %A MacLeod, Catherine A %A Maier, Wolfgang %A Mangialasche, Francesca %A Spallazzi, Marco %A Marquié, Marta %A Marshall, Rachel %A Martin, Eden R %A Montes, Angel Martín %A Rodríguez, Carmen Martínez %A Masullo, Carlo %A Mayeux, Richard %A Mead, Simon %A Mecocci, Patrizia %A Medina, Miguel %A Meggy, Alun %A Mehrabian, Shima %A Mendoza, Silvia %A Menéndez-González, Manuel %A Mir, Pablo %A Moebus, Susanne %A Mol, Merel %A Molina-Porcel, Laura %A Montrreal, Laura %A Morelli, Laura %A Moreno, Fermin %A Morgan, Kevin %A Mosley, Thomas %A Nöthen, Markus M %A Muchnik, Carolina %A Mukherjee, Shubhabrata %A Nacmias, Benedetta %A Ngandu, Tiia %A Nicolas, Gaël %A Nordestgaard, Børge G %A Olaso, Robert %A Orellana, Adelina %A Orsini, Michela %A Ortega, Gemma %A Padovani, Alessandro %A Paolo, Caffarra %A Papenberg, Goran %A Parnetti, Lucilla %A Pasquier, Florence %A Pastor, Pau %A Peloso, Gina %A Pérez-Cordón, Alba %A Pérez-Tur, Jordi %A Pericard, Pierre %A Peters, Oliver %A Pijnenburg, Yolande A L %A Pineda, Juan A %A Piñol-Ripoll, Gerard %A Pisanu, Claudia %A Polak, Thomas %A Popp, Julius %A Posthuma, Danielle %A Priller, Josef %A Puerta, Raquel %A Quenez, Olivier %A Quintela, Inés %A Thomassen, Jesper Qvist %A Rábano, Alberto %A Rainero, Innocenzo %A Rajabli, Farid %A Ramakers, Inez %A Real, Luis M %A Reinders, Marcel J T %A Reitz, Christiane %A Reyes-Dumeyer, Dolly %A Ridge, Perry %A Riedel-Heller, Steffi %A Riederer, Peter %A Roberto, Natalia %A Rodriguez-Rodriguez, Eloy %A Rongve, Arvid %A Allende, Irene Rosas %A Rosende-Roca, Maitée %A Royo, Jose Luís %A Rubino, Elisa %A Rujescu, Dan %A Sáez, María Eugenia %A Sakka, Paraskevi %A Saltvedt, Ingvild %A Sanabria, Ángela %A Sánchez-Arjona, María Bernal %A Sanchez-Garcia, Florentino %A Juan, Pascual Sánchez %A Sánchez-Valle, Raquel %A Sando, Sigrid B %A Sarnowski, Chloe %A Satizabal, Claudia L %A Scamosci, Michela %A Scarmeas, Nikolaos %A Scarpini, Elio %A Scheltens, Philip %A Scherbaum, Norbert %A Scherer, Martin %A Schmid, Matthias %A Schneider, Anja %A Schott, Jonathan M %A Selbæk, Geir %A Seripa, Davide %A Serrano, Manuel %A Sha, Jin %A Shadrin, Alexey A %A Skrobot, Olivia %A Slifer, Susan %A Snijders, Gijsje J L %A Soininen, Hilkka %A Solfrizzi, Vincenzo %A Solomon, Alina %A Song, Yeunjoo %A Sorbi, Sandro %A Sotolongo-Grau, Oscar %A Spalletta, Gianfranco %A Spottke, Annika %A Squassina, Alessio %A Stordal, Eystein %A Tartan, Juan Pablo %A Tarraga, Lluis %A Tesi, Niccolo %A Thalamuthu, Anbupalam %A Thomas, Tegos %A Tosto, Giuseppe %A Traykov, Latchezar %A Tremolizzo, Lucio %A Tybjærg-Hansen, Anne %A Uitterlinden, Andre %A Ullgren, Abbe %A Ulstein, Ingun %A Valero, Sergi %A Valladares, Otto %A Broeckhoven, Christine Van %A Vance, Jeffery %A Vardarajan, Badri N %A van der Lugt, Aad %A Dongen, Jasper Van %A van Rooij, Jeroen %A van Swieten, John %A Vandenberghe, Rik %A Verhey, Frans %A Vidal, Jean-Sebastien %A Vogelgsang, Jonathan %A Vyhnalek, Martin %A Wagner, Michael %A Wallon, David %A Wang, Li-San %A Wang, Ruiqi %A Weinhold, Leonie %A Wiltfang, Jens %A Windle, Gill %A Woods, Bob %A Yannakoulia, Mary %A Zare, Habil %A Zhao, Yi %A Zhang, Xiaoling %A Zhu, Congcong %A Zulaica, Miren %A Farrer, Lindsay A %A Psaty, Bruce M %A Ghanbari, Mohsen %A Raj, Towfique %A Sachdev, Perminder %A Mather, Karen %A Jessen, Frank %A Ikram, M Arfan %A de Mendonça, Alexandre %A Hort, Jakub %A Tsolaki, Magda %A Pericak-Vance, Margaret A %A Amouyel, Philippe %A Williams, Julie %A Frikke-Schmidt, Ruth %A Clarimon, Jordi %A Deleuze, Jean-François %A Rossi, Giacomina %A Seshadri, Sudha %A Andreassen, Ole A %A Ingelsson, Martin %A Hiltunen, Mikko %A Sleegers, Kristel %A Schellenberg, Gerard D %A van Duijn, Cornelia M %A Sims, Rebecca %A van der Flier, Wiesje M %A Ruiz, Agustin %A Ramirez, Alfredo %A Lambert, Jean-Charles %K Alzheimer Disease %K Cognitive Dysfunction %K Genome-Wide Association Study %K Humans %K tau Proteins %X

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.

%B Nat Genet %V 54 %P 412-436 %8 2022 Apr %G eng %N 4 %1 https://www.ncbi.nlm.nih.gov/pubmed/35379992?dopt=Abstract %R 10.1038/s41588-022-01024-z %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 2018 %T Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes. %A Mahajan, Anubha %A Wessel, Jennifer %A Willems, Sara M %A Zhao, Wei %A Robertson, Neil R %A Chu, Audrey Y %A Gan, Wei %A Kitajima, Hidetoshi %A Taliun, Daniel %A Rayner, N William %A Guo, Xiuqing %A Lu, Yingchang %A Li, Man %A Jensen, Richard A %A Hu, Yao %A Huo, Shaofeng %A Lohman, Kurt K %A Zhang, Weihua %A Cook, James P %A Prins, Bram Peter %A Flannick, Jason %A Grarup, Niels %A Trubetskoy, Vassily Vladimirovich %A Kravic, Jasmina %A Kim, Young Jin %A Rybin, Denis V %A Yaghootkar, Hanieh %A Müller-Nurasyid, Martina %A Meidtner, Karina %A Li-Gao, Ruifang %A Varga, Tibor V %A Marten, Jonathan %A Li, Jin %A Smith, Albert Vernon %A An, Ping %A Ligthart, Symen %A Gustafsson, Stefan %A Malerba, Giovanni %A Demirkan, Ayse %A Tajes, Juan Fernandez %A Steinthorsdottir, Valgerdur %A Wuttke, Matthias %A Lecoeur, Cécile %A Preuss, Michael %A Bielak, Lawrence F %A Graff, Marielisa %A Highland, Heather M %A Justice, Anne E %A Liu, Dajiang J %A Marouli, Eirini %A Peloso, Gina Marie %A Warren, Helen R %A Afaq, Saima %A Afzal, Shoaib %A Ahlqvist, Emma %A Almgren, Peter %A Amin, Najaf %A Bang, Lia B %A Bertoni, Alain G %A Bombieri, Cristina %A Bork-Jensen, Jette %A Brandslund, Ivan %A Brody, Jennifer A %A Burtt, Noël P %A Canouil, Mickaël %A Chen, Yii-Der Ida %A Cho, Yoon Shin %A Christensen, Cramer %A Eastwood, Sophie V %A Eckardt, Kai-Uwe %A Fischer, Krista %A Gambaro, Giovanni %A Giedraitis, Vilmantas %A Grove, Megan L %A de Haan, Hugoline G %A Hackinger, Sophie %A Hai, Yang %A Han, Sohee %A Tybjærg-Hansen, Anne %A Hivert, Marie-France %A Isomaa, Bo %A Jäger, Susanne %A Jørgensen, Marit E %A Jørgensen, Torben %A Käräjämäki, Annemari %A Kim, Bong-Jo %A Kim, Sung Soo %A Koistinen, Heikki A %A Kovacs, Peter %A Kriebel, Jennifer %A Kronenberg, Florian %A Läll, Kristi %A Lange, Leslie A %A Lee, Jung-Jin %A Lehne, Benjamin %A Li, Huaixing %A Lin, Keng-Hung %A Linneberg, Allan %A Liu, Ching-Ti %A Liu, Jun %A Loh, Marie %A Mägi, Reedik %A Mamakou, Vasiliki %A McKean-Cowdin, Roberta %A Nadkarni, Girish %A Neville, Matt %A Nielsen, Sune F %A Ntalla, Ioanna %A Peyser, Patricia A %A Rathmann, Wolfgang %A Rice, Kenneth %A Rich, Stephen S %A Rode, Line %A Rolandsson, Olov %A Schönherr, Sebastian %A Selvin, Elizabeth %A Small, Kerrin S %A Stančáková, Alena %A Surendran, Praveen %A Taylor, Kent D %A Teslovich, Tanya M %A Thorand, Barbara %A Thorleifsson, Gudmar %A Tin, Adrienne %A Tonjes, Anke %A Varbo, Anette %A Witte, Daniel R %A Wood, Andrew R %A Yajnik, Pranav %A Yao, Jie %A Yengo, Loic %A Young, Robin %A Amouyel, Philippe %A Boeing, Heiner %A Eric Boerwinkle %A Bottinger, Erwin P %A Chowdhury, Rajiv %A Collins, Francis S %A Dedoussis, George %A Dehghan, Abbas %A Deloukas, Panos %A Ferrario, Marco M %A Ferrieres, Jean %A Florez, Jose C %A Frossard, Philippe %A Gudnason, Vilmundur %A Harris, Tamara B %A Heckbert, Susan R %A Howson, Joanna M M %A Ingelsson, Martin %A Kathiresan, Sekar %A Kee, Frank %A Kuusisto, Johanna %A Langenberg, Claudia %A Launer, Lenore J %A Lindgren, Cecilia M %A Männistö, Satu %A Meitinger, Thomas %A Melander, Olle %A Mohlke, Karen L %A Moitry, Marie %A Morris, Andrew D %A Murray, Alison D %A de Mutsert, Renée %A Orho-Melander, Marju %A Owen, Katharine R %A Perola, Markus %A Peters, Annette %A Province, Michael A %A Rasheed, Asif %A Ridker, Paul M %A Rivadineira, Fernando %A Rosendaal, Frits R %A Rosengren, Anders H %A Salomaa, Veikko %A Sheu, Wayne H-H %A Sladek, Rob %A Smith, Blair H %A Strauch, Konstantin %A Uitterlinden, André G %A Varma, Rohit %A Willer, Cristen J %A Blüher, Matthias %A Butterworth, Adam S %A Chambers, John Campbell %A Chasman, Daniel I %A Danesh, John %A van Duijn, Cornelia %A Dupuis, Josée %A Franco, Oscar H %A Franks, Paul W %A Froguel, Philippe %A Grallert, Harald %A Groop, Leif %A Han, Bok-Ghee %A Hansen, Torben %A Hattersley, Andrew T %A Hayward, Caroline %A Ingelsson, Erik %A Kardia, Sharon L R %A Karpe, Fredrik %A Kooner, Jaspal Singh %A Köttgen, Anna %A Kuulasmaa, Kari %A Laakso, Markku %A Lin, Xu %A Lind, Lars %A Liu, Yongmei %A Loos, Ruth J F %A Marchini, Jonathan %A Metspalu, Andres %A Mook-Kanamori, Dennis %A Nordestgaard, Børge G %A Palmer, Colin N A %A Pankow, James S %A Pedersen, Oluf %A Psaty, Bruce M %A Rauramaa, Rainer %A Sattar, Naveed %A Schulze, Matthias B %A Soranzo, Nicole %A Spector, Timothy D %A Stefansson, Kari %A Stumvoll, Michael %A Thorsteinsdottir, Unnur %A Tuomi, Tiinamaija %A Tuomilehto, Jaakko %A Wareham, Nicholas J %A Wilson, James G %A Zeggini, Eleftheria %A Scott, Robert A %A Barroso, Inês %A Frayling, Timothy M %A Goodarzi, Mark O %A Meigs, James B %A Boehnke, Michael %A Saleheen, Danish %A Morris, Andrew P %A Rotter, Jerome I %A McCarthy, Mark I %K Alleles %K Chromosome Mapping %K Diabetes Mellitus, Type 2 %K Exome Sequencing %K Female %K Genetic Predisposition to Disease %K Genetic Variation %K Genome-Wide Association Study %K Humans %K Male %K White People %X

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.

%B Nat Genet %V 50 %P 559-571 %8 2018 Apr %G eng %N 4 %1 https://www.ncbi.nlm.nih.gov/pubmed/29632382?dopt=Abstract %R 10.1038/s41588-018-0084-1 %0 Journal Article %J Nat Genet %D 2017 %T Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. %A Howson, Joanna M M %A Zhao, Wei %A Barnes, Daniel R %A Ho, Weang-Kee %A Young, Robin %A Paul, Dirk S %A Waite, Lindsay L %A Freitag, Daniel F %A Fauman, Eric B %A Salfati, Elias L %A Sun, Benjamin B %A Eicher, John D %A Johnson, Andrew D %A Sheu, Wayne H H %A Nielsen, Sune F %A Lin, Wei-Yu %A Surendran, Praveen %A Mälarstig, Anders %A Wilk, Jemma B %A Tybjærg-Hansen, Anne %A Rasmussen, Katrine L %A Kamstrup, Pia R %A Deloukas, Panos %A Erdmann, Jeanette %A Kathiresan, Sekar %A Samani, Nilesh J %A Schunkert, Heribert %A Watkins, Hugh %A Do, Ron %A Rader, Daniel J %A Johnson, Julie A %A Hazen, Stanley L %A Quyyumi, Arshed A %A Spertus, John A %A Pepine, Carl J %A Franceschini, Nora %A Justice, Anne %A Reiner, Alex P %A Buyske, Steven %A Hindorff, Lucia A %A Carty, Cara L %A North, Kari E %A Kooperberg, Charles %A Eric Boerwinkle %A Young, Kristin %A Graff, Mariaelisa %A Peters, Ulrike %A Absher, Devin %A Hsiung, Chao A %A Lee, Wen-Jane %A Taylor, Kent D %A Chen, Ying-Hsiang %A Lee, I-Te %A Guo, Xiuqing %A Chung, Ren-Hua %A Hung, Yi-Jen %A Rotter, Jerome I %A Juang, Jyh-Ming J %A Quertermous, Thomas %A Wang, Tzung-Dau %A Rasheed, Asif %A Frossard, Philippe %A Alam, Dewan S %A Majumder, Abdulla Al Shafi %A Di Angelantonio, Emanuele %A Chowdhury, Rajiv %A Chen, Yii-Der Ida %A Nordestgaard, Børge G %A Assimes, Themistocles L %A Danesh, John %A Butterworth, Adam S %A Saleheen, Danish %K Arteries %K Atherosclerosis %K Cell Adhesion %K Chemotaxis, Leukocyte %K Coronary Artery Disease %K Energy Metabolism %K Female %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Genotype %K Histone Code %K Humans %K Male %K Muscle, Smooth, Vascular %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Risk Factors %X

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10, in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.

%B Nat Genet %V 49 %P 1113-1119 %8 2017 Jul %G eng %N 7 %1 https://www.ncbi.nlm.nih.gov/pubmed/28530674?dopt=Abstract %R 10.1038/ng.3874