| Title: |
Common variants in Alzheimer's disease and risk stratification by polygenic risk scores |
| Authors: |
de Rojas, I; Moreno-Grau, S; Tesi, N; Grenier-Boley, B; Andrade, V; Jansen, I; Pedersen, N; Stringa, N; Zettergren, A; Hernández, I; Montrreal, L; Antúnez, C; Antonell, A; Tankard, R; Bis, J; Sims, R; Bellenguez, C; Quintela, I; González-Perez, A; Calero, M; Franco-Macías, E; Macías, J; Blesa, R; Cervera-Carles, L; Menéndez-González, M; Frank-García, A; Royo, J; Moreno, F; Huerto Vilas, R; Baquero, M; Diez-Fairen, M; Lage, C; García-Madrona, S; García-González, P; Alarcón-Martín, E; Valero, S; Sotolongo-Grau, O; Ullgren, A; Naj, A; Lemstra, A; Benaque, A; Pérez-Cordón, A; Benussi, A; Rábano, A; Padovani, A; Squassina, A; de Mendonça, A; Arias Pastor, A; Kok, A; Meggy, A; Pastor, A; Espinosa, A; Corma-Gómez, A; Martín Montes, A; Sanabria, Á; Destefano, A; Schneider, A; Haapasalo, A; Kinhult Ståhlbom, A; Tybjærg-Hansen, A; Hartmann, A; Spottke, A; Corbatón-Anchuelo, A; Rongve, A; Borroni, B; Arosio, B; Nacmias, B; Nordestgaard, B; Kunkle, B; Charbonnier, C; Abdelnour, C; Masullo, C; Martínez Rodríguez, C; Muñoz-Fernandez, C; Dufouil, C; Graff, C; Ferreira, C; Chillotti, C; Reynolds, C; Fenoglio, C; Van Broeckhoven, C; Clark, C; Pisanu, C; Satizabal, C; Holmes, C; Buiza-Rueda, D; Aarsland, D; Rujescu, D; Alcolea, D; Galimberti, D; Wallon, D; Seripa, D; Grünblatt, E; Dardiotis, E; Düzel, E; Scarpini, E; Conti, E; Rubino, E; Gelpi, E; Rodriguez-Rodriguez, E; Duron, E; Boerwinkle, E; Ferri, E; Tagliavini, F; Küçükali, F; Pasquier, F; Sanchez-Garcia, F; Mangialasche, F; Jessen, F; Nicolas, G; Selbæk, G; Ortega, G; Chêne, G; Hadjigeorgiou, G; Rossi, G; Spalletta, G; Giaccone, G; Grande, G; Binetti, G; Papenberg, G; Hampel, H; Bailly, H; Zetterberg, H; Soininen, H; Karlsson, I; Alvarez, I; Appollonio, I; Giegling, I; Skoog, I; Saltvedt, I; Rainero, I; Rosas Allende, I; Hort, J; Diehl-Schmid, J; Van Dongen, J; Vidal, J; Lehtisalo, J; Wiltfang, J; Thomassen, J; Kornhuber, J; Haines, J; Vogelgsang, J; Pineda, J; Fortea, J; Popp, J; Deckert, J; Buerger, K; Morgan, K; Fließbach, K; Sleegers, K; Molina-Porcel, L; Kilander, L; Weinhold, L; Farrer, L; Wang, L; Kleineidam, L; Farotti, L; Parnetti, L; Tremolizzo, L; Hausner, L; Benussi, L; Froelich, L; Ikram, M; Deniz-Naranjo, M; Tsolaki, M; Rosende-Roca, M; Löwenmark, M; Hulsman, M; Spallazzi, M; Pericak-Vance, M; Esiri, M; Bernal Sánchez-Arjona, M; Dalmasso, M; Martínez-Larrad, M; Arcaro, M; Nöthen, M; Fernández-Fuertes, M; Dichgans, M; Ingelsson, M; Herrmann, M; Scherer, M; Vyhnalek, M; Kosmidis, M; Yannakoulia, M; Schmid, M; Ewers, M; Heneka, M; Wagner, M; Scamosci, M; Kivipelto, M; Hiltunen, M; Zulaica, M; Alegret, M; Fornage, M; Roberto, N; van Schoor, N; Seidu, N; Banaj, N; Armstrong, N; Scarmeas, N; Scherbaum, N; Goldhardt, O; Hanon, O; Peters, O; Skrobot, O; Quenez, O; Lerch, O; Bossù, P; Caffarra, P; Dionigi Rossi, P; Sakka, P; Hoffmann, P; Holmans, P; Fischer, P; Riederer, P; Yang, Q; Marshall, R; Kalaria, R; Mayeux, R; Vandenberghe, R; Cecchetti, R; Ghidoni, R; Frikke-Schmidt, R; Sorbi, S; Hägg, S; Engelborghs, S; Helisalmi, S; Botne Sando, S; Kern, S; Archetti, S; Boschi, S; Fostinelli, S; Gil, S; Mendoza, S; Mead, S; Ciccone, S; Djurovic, S; Heilmann-Heimbach, S; Riedel-Heller, S; Kuulasmaa, T; Del Ser, T; Lebouvier, T; Polak, T; Ngandu, T; Grimmer, T; Bessi, V; Escott-Price, V; Giedraitis, V; Deramecourt, V; Maier, W; Jian, X; Pijnenburg, Y; Andreoni, S; Ferrarese, C; Sala, G; Zoia, C; Kehoe, P; Garcia-Ribas, G; Sánchez-Juan, P; Pastor, P; Pérez-Tur, J; Piñol-Ripoll, G; Lopez de Munain, A; García-Alberca, J; Bullido, M; Álvarez, V; Lleó, A; Real, L; Mir, P; Medina, M; Scheltens, P; Holstege, H; Marquié, M; Sáez, M; Carracedo, Á; Amouyel, P; Schellenberg, G; Williams, J; Seshadri, S; van Duijn, C; Mather, K; Sánchez-Valle, R; Serrano-Ríos, M; Orellana, A; Tárraga, L; Blennow, K; Huisman, M; Andreassen, O; Posthuma, D; Clarimón, J; Boada, M; van der Flier, W; Ramirez, A; Lambert, J; van der Lee, S; Ruiz, A; de Rojas, Itziar; Moreno-Grau, Sonia; Tesi, Niccolo; Grenier-Boley, Benjamin; Andrade, Victor; Jansen, Iris E; Pedersen, Nancy L; Stringa, Najada; Zettergren, Anna; Hernández, Isabel; Montrreal, Laura; Antúnez, Carmen; Antonell, Anna; Tankard, Rick M; Bis, Joshua C; Sims, Rebecca; Bellenguez, Céline; Quintela, Inés; González-Perez, Antonio; Calero, Miguel; Franco-Macías, Emilio; Macías, Juan; Blesa, Rafael; Cervera-Carles, Laura; Menéndez-González, Manuel; Frank-García, Ana; Royo, Jose Luís; Moreno, Fermin; Huerto Vilas, Raquel; Baquero, Miquel; Diez-Fairen, Mónica; Lage, Carmen; García-Madrona, Sebastián; García-González, Pablo; Alarcón-Martín, Emilio; Valero, Sergi; Sotolongo-Grau, Oscar; Ullgren, Abbe; Naj, Adam C; Lemstra, Afina W; Benaque, Alba; Pérez-Cordón, Alba; Benussi, Alberto; Rábano, Alberto; Padovani, Alessandro; Squassina, Alessio; de Mendonça, Alexandre; Arias Pastor, Alfonso; Kok, Almar A L; Meggy, Alun; Pastor, Ana Belén; Espinosa, Ana; Corma-Gómez, Anas; Martín Montes, Angel; Sanabria, Ángela; DeStefano, Anita L; Schneider, Anja; Haapasalo, Annakaisa; Kinhult Ståhlbom, Anne; Tybjærg-Hansen, Anne; Hartmann, Annette M; Spottke, Annika; Corbatón-Anchuelo, Arturo; Rongve, Arvid; Borroni, Barbara; Arosio, Beatrice; Nacmias, Benedetta; Nordestgaard, Børge G; Kunkle, Brian W; Charbonnier, Camille; Abdelnour, Carla; Masullo, Carlo; Martínez Rodríguez, Carmen; Muñoz-Fernandez, Carmen; Dufouil, Carole; Graff, Caroline; Ferreira, Catarina B; Chillotti, Caterina; Reynolds, Chandra A; Fenoglio, Chiara; Van Broeckhoven, Christine; Clark, Christopher; Pisanu, Claudia; Satizabal, Claudia L; Holmes, Clive; Buiza-Rueda, Dolores; Aarsland, Dag; Rujescu, Dan; Alcolea, Daniel; Galimberti, Daniela; Wallon, David; Seripa, Davide; Grünblatt, Edna; Dardiotis, Efthimios; Düzel, Emrah; Scarpini, Elio; Conti, Elisa; Rubino, Elisa; Gelpi, Ellen; Rodriguez-Rodriguez, Eloy; Duron, Emmanuelle; Boerwinkle, Eric; Ferri, Evelyn; Tagliavini, Fabrizio; Küçükali, Fahri; Pasquier, Florence; Sanchez-Garcia, Florentino; Mangialasche, Francesca; Jessen, Frank; Nicolas, Gaël; Selbæk, Geir; Ortega, Gemma; Chêne, Geneviève; Hadjigeorgiou, Georgios; Rossi, Giacomina; Spalletta, Gianfranco; Giaccone, Giorgio; Grande, Giulia; Binetti, Giuliano; Papenberg, Goran; Hampel, Harald; Bailly, Henri; Zetterberg, Henrik; Soininen, Hilkka; Karlsson, Ida K; Alvarez, Ignacio; Appollonio, Ildebrando; Giegling, Ina; Skoog, Ingmar; Saltvedt, Ingvild; Rainero, Innocenzo; Rosas Allende, Irene; Hort, Jakub; Diehl-Schmid, Janine; Van Dongen, Jasper; Vidal, Jean-Sebastien; Lehtisalo, Jenni; Wiltfang, Jens; Thomassen, Jesper Qvist; Kornhuber, Johannes; Haines, Jonathan L; Vogelgsang, Jonathan; Pineda, Juan A; Fortea, Juan; Popp, Julius; Deckert, Jürgen; Buerger, Katharina; Morgan, Kevin; Fließbach, Klaus; Sleegers, Kristel; Molina-Porcel, Laura; Kilander, Lena; Weinhold, Leonie; Farrer, Lindsay A; Wang, Li-San; Kleineidam, Luca; Farotti, Lucia; Parnetti, Lucilla; Tremolizzo, Lucio; Hausner, Lucrezia; Benussi, Luisa; Froelich, Lutz; Ikram, M Arfan; Deniz-Naranjo, M Candida; Tsolaki, Magda; Rosende-Roca, Maitée; Löwenmark, Malin; Hulsman, Marc; Spallazzi, Marco; Pericak-Vance, Margaret A; Esiri, Margaret; Bernal Sánchez-Arjona, María; Dalmasso, Maria Carolina; Martínez-Larrad, María Teresa; Arcaro, Marina; Nöthen, Markus M; Fernández-Fuertes, Marta; Dichgans, Martin; Ingelsson, Martin; Herrmann, Martin J; Scherer, Martin; Vyhnalek, Martin; Kosmidis, Mary H; Yannakoulia, Mary; Schmid, Matthias; Ewers, Michael; Heneka, Michael T; Wagner, Michael; Scamosci, Michela; Kivipelto, Miia; Hiltunen, Mikko; Zulaica, Miren; Alegret, Montserrat; Fornage, Myriam; Roberto, Natalia; van Schoor, Natasja M; Seidu, Nazib M; Banaj, Nerisa; Armstrong, Nicola J; Scarmeas, Nikolaos; Scherbaum, Norbert; Goldhardt, Oliver; Hanon, Oliver; Peters, Oliver; Skrobot, Olivia Anna; Quenez, Olivier; Lerch, Ondrej; Bossù, Paola; Caffarra, Paolo; Dionigi Rossi, Paolo; Sakka, Paraskevi; Hoffmann, Per; Holmans, Peter A; Fischer, Peter; Riederer, Peter; Yang, Qiong; Marshall, Rachel; Kalaria, Rajesh N; Mayeux, Richard; Vandenberghe, Rik; Cecchetti, Roberta; Ghidoni, Roberta; Frikke-Schmidt, Ruth; Sorbi, Sandro; Hägg, Sara; Engelborghs, Sebastiaan; Helisalmi, Seppo; Botne Sando, Sigrid; Kern, Silke; Archetti, Silvana; Boschi, Silvia; Fostinelli, Silvia; Gil, Silvia; Mendoza, Silvia; Mead, Simon; Ciccone, Simona; Djurovic, Srdjan; Heilmann-Heimbach, Stefanie; Riedel-Heller, Steffi; Kuulasmaa, Teemu; Del Ser, Teodoro; Lebouvier, Thibaud; Polak, Thomas; Ngandu, Tiia; Grimmer, Timo; Bessi, Valentina; Escott-Price, Valentina; Giedraitis, Vilmantas; Deramecourt, Vincent; Maier, Wolfgang; Jian, Xueqiu; Pijnenburg, Yolande A L; Andreoni, Simona; Ferrarese, Carlo; Sala Gessica; Zoia, Chiara Paola; Kehoe, Patrick Gavin; Garcia-Ribas, Guillermo; Sánchez-Juan, Pascual; Pastor, Pau; Pérez-Tur, Jordi; Piñol-Ripoll, Gerard; Lopez de Munain, Adolfo; García-Alberca, Jose María; Bullido, María J; Álvarez, Victoria; Lleó, Alberto; Real, Luis M; Mir, Pablo; Medina, Miguel; Scheltens, Philip; Holstege, Henne; Marquié, Marta; Sáez, María Eugenia; Carracedo, Ángel; Amouyel, Philippe; Schellenberg, Gerard D; Williams, Julie; Seshadri, Sudha; van Duijn, Cornelia M; Mather, Karen A; Sánchez-Valle, Raquel; Serrano-Ríos, Manuel; Orellana, Adelina; Tárraga, Lluís; Blennow, Kaj; Huisman, Martijn; Andreassen, Ole A; Posthuma, Danielle; Clarimón, Jordi; Boada, Mercè; van der Flier, Wiesje M; Ramirez, Alfredo; Lambert, Jean-Charles; van der Lee, Sven J; Ruiz, Agustín |
| Publisher Information: |
Nature Publishing Group country:GB 2021 |
| Document Type: |
Electronic Resource |
| Abstract: |
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. |
| Index Terms: |
Alzheimer's disease; genetic; association study; APOE; amyloid; MED/26 - NEUROLOGIA; info:eu-repo/semantics/article |
| URL: |
http://hdl.handle.net/10281/316630; info:eu-repo/semantics/altIdentifier/pmid/34099642; info:eu-repo/semantics/altIdentifier/wos/WOS:000713875100002; volume:12; issue:1; journal:NATURE COMMUNICATIONS |
| Availability: |
Open access content. Open access content; info:eu-repo/semantics/openAccess |
| Note: |
ELETTRONICO; English |
| Other Numbers: |
ITBAO oai:boa.unimib.it:10281/316630; 10.1038/s41467-021-22491-8; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85107895788; 1308939546 |
| Contributing Source: |
BICOCCA OPEN ARCH; From OAIster®, provided by the OCLC Cooperative. |
| Accession Number: |
edsoai.on1308939546 |
| Database: |
OAIster |