Медицинская библиотека · Nature genetics · 2022

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Bellenguez Céline, Küçükali Fahri, Jansen Iris E, Kleineidam Luca, Moreno-Grau Sonia, Amin Najaf, Naj Adam C, Campos-Martin Rafael, Grenier-Boley Benjamin, Andrade Victor, Holmans Peter A, Boland Anne, Damotte Vincent, van der Lee Sven J, Costa Marcos R, Kuulasmaa Teemu, Yang Qiong, de Rojas Itziar, Bis Joshua C, Yaqub Amber, Prokic Ivana, Chapuis Julien, Ahmad Shahzad, Giedraitis Vilmantas, Aarsland Dag, Garcia-Gonzalez Pablo, Abdelnour Carla, Alarcón-Martín Emilio, Alcolea Daniel, Alegret Montserrat, Alvarez Ignacio, Álvarez Victoria, Armstrong Nicola J, Tsolaki Anthoula, Antúnez Carmen, Appollonio Ildebrando, Arcaro Marina, Archetti Silvana, Pastor Alfonso Arias, Arosio Beatrice, Athanasiu Lavinia, Bailly Henri, Banaj Nerisa, Baquero Miquel, Barral Sandra, Beiser Alexa, Pastor Ana Belén, Below Jennifer E, Benchek Penelope, Benussi Luisa, Berr Claudine, Besse Céline, Bessi Valentina, Binetti Giuliano, Bizarro Alessandra, Blesa Rafael, Boada Mercè, Boerwinkle Eric, Borroni Barbara, Boschi Silvia, Bossù Paola, Bråthen Geir, Bressler Jan, Bresner Catherine, Brodaty Henry, Brookes Keeley J, Brusco Luis Ignacio, Buiza-Rueda Dolores, Bûrger Katharina, Burholt Vanessa, Bush William S, Calero Miguel, Cantwell Laura B, Chene Geneviève, Chung Jaeyoon, Cuccaro Michael L, Carracedo Ángel, Cecchetti Roberta, Cervera-Carles Laura, Charbonnier Camille, Chen Hung-Hsin, Chillotti Caterina, Ciccone Simona, Claassen Jurgen A H R, Clark Christopher, Conti Elisa, Corma-Gómez Anaïs, Costantini Emanuele, Custodero Carlo, Daian Delphine, Dalmasso Maria Carolina, Daniele Antonio, Dardiotis Efthimios, Dartigues Jean-François, de Deyn Peter Paul, de Paiva Lopes Katia, de Witte Lot D, Debette Stéphanie, Deckert Jürgen, Del Ser Teodoro, Denning Nicola, DeStefano Anita, Dichgans Martin, Diehl-Schmid Janine, Diez-Fairen Mónica, Rossi Paolo Dionigi, Djurovic Srdjan, Duron Emmanuelle, Düzel Emrah, Dufouil Carole, Eiriksdottir Gudny, Engelborghs Sebastiaan, Escott-Price Valentina, Espinosa Ana, Ewers Michael, Faber Kelley M, Fabrizio Tagliavini, Nielsen Sune Fallgaard, Fardo David W, Farotti Lucia, Fenoglio Chiara, Fernández-Fuertes Marta, Ferrari Raffaele, Ferreira Catarina B, Ferri Evelyn, Fin Bertrand, Fischer Peter, Fladby Tormod, Fließbach Klaus, Fongang Bernard, Fornage Myriam, Fortea Juan, Foroud Tatiana M, Fostinelli Silvia, Fox Nick C, Franco-Macías Emlio, Bullido María J, Frank-García Ana, Froelich Lutz, Fulton-Howard Brian, Galimberti Daniela, García-Alberca Jose Maria, García-González Pablo, Garcia-Madrona Sebastian, Garcia-Ribas Guillermo, Ghidoni Roberta, Giegling Ina, Giorgio Giaccone, Goate Alison M, Goldhardt Oliver, Gomez-Fonseca Duber, González-Pérez Antonio, Graff Caroline, Grande Giulia, Green Emma, Grimmer Timo, Grünblatt Edna, Grunin Michelle, Gudnason Vilmundur, Guetta-Baranes Tamar, Haapasalo Annakaisa, Hadjigeorgiou Georgios, Haines Jonathan L, Hamilton-Nelson Kara L, Hampel Harald, Hanon Olivier, Hardy John, Hartmann Annette M, Hausner Lucrezia, Harwood Janet, Heilmann-Heimbach Stefanie, Helisalmi Seppo, Heneka Michael T, Hernández Isabel, Herrmann Martin J, Hoffmann Per, Holmes Clive, Holstege Henne, Vilas Raquel Huerto, Hulsman Marc, Humphrey Jack, Biessels Geert Jan, Jian Xueqiu, Johansson Charlotte, Jun Gyungah R, Kastumata Yuriko, Kauwe John, Kehoe Patrick G, Kilander Lena, Ståhlbom Anne Kinhult, Kivipelto Miia, Koivisto Anne, Kornhuber Johannes, Kosmidis Mary H, Kukull Walter A, Kuksa Pavel P, Kunkle Brian W, Kuzma Amanda B, Lage Carmen, Laukka Erika J, Launer Lenore, Lauria Alessandra, Lee Chien-Yueh, Lehtisalo Jenni, Lerch Ondrej, Lleó Alberto, Longstreth William, Lopez Oscar, de Munain Adolfo Lopez, Love Seth, Löwemark Malin, Luckcuck Lauren, Lunetta Kathryn L, Ma Yiyi, Macías Juan, MacLeod Catherine A, Maier Wolfgang, Mangialasche Francesca, Spallazzi Marco, Marquié Marta, Marshall Rachel, Martin Eden R, Montes Angel Martín, Rodríguez Carmen Martínez, Masullo Carlo, Mayeux Richard, Mead Simon, Mecocci Patrizia, Medina Miguel, Meggy Alun, Mehrabian Shima, Mendoza Silvia, Menéndez-González Manuel, Mir Pablo, Moebus Susanne, Mol Merel, Molina-Porcel Laura, Montrreal Laura, Morelli Laura, Moreno Fermin, Morgan Kevin, Mosley Thomas, Nöthen Markus M, Muchnik Carolina, Mukherjee Shubhabrata, Nacmias Benedetta, Ngandu Tiia, Nicolas Gael, Nordestgaard Børge G, Olaso Robert, Orellana Adelina, Orsini Michela, Ortega Gemma, Padovani Alessandro, Paolo Caffarra, Papenberg Goran, Parnetti Lucilla, Pasquier Florence, Pastor Pau, Peloso Gina, Pérez-Cordón Alba, Pérez-Tur Jordi, Pericard Pierre, Peters Oliver, Pijnenburg Yolande A L, Pineda Juan A, Piñol-Ripoll Gerard, Pisanu Claudia, Polak Thomas, Popp Julius, Posthuma Danielle, Priller Josef, Puerta Raquel, Quenez Olivier, Quintela Inés, Thomassen Jesper Qvist, Rábano Alberto, Rainero Innocenzo, Rajabli Farid, Ramakers Inez, Real Luis M, Reinders Marcel J T, Reitz Christiane, Reyes-Dumeyer Dolly, Ridge Perry, Riedel-Heller Steffi, Riederer Peter, Roberto Natalia, Rodriguez-Rodriguez Eloy, Rongve Arvid, Allende Irene Rosas, Rosende-Roca Maitée, Royo Jose Luis, Rubino Elisa, Rujescu Dan, Sáez María Eugenia, Sakka Paraskevi, Saltvedt Ingvild, Sanabria Ángela, Sánchez-Arjona María Bernal, Sanchez-Garcia Florentino, Juan Pascual Sánchez, Sánchez-Valle Raquel, Sando Sigrid B, Sarnowski Chloé, Satizabal Claudia L, Scamosci Michela, Scarmeas Nikolaos, Scarpini Elio, Scheltens Philip, Scherbaum Norbert, Scherer Martin, Schmid Matthias, Schneider Anja, Schott Jonathan M, Selbæk Geir, Seripa Davide, Serrano Manuel, Sha Jin, Shadrin Alexey A, Skrobot Olivia, Slifer Susan, Snijders Gijsje J L, Soininen Hilkka, Solfrizzi Vincenzo, Solomon Alina, Song Yeunjoo, Sorbi Sandro, Sotolongo-Grau Oscar, Spalletta Gianfranco, Spottke Annika, Squassina Alessio, Stordal Eystein, Tartan Juan Pablo, Tárraga Lluís, Tesí Niccolo, Thalamuthu Anbupalam, Thomas Tegos, Tosto Giuseppe, Traykov Latchezar, Tremolizzo Lucio, Tybjærg-Hansen Anne, Uitterlinden Andre, Ullgren Abbe, Ulstein Ingun, Valero Sergi, Valladares Otto, Broeckhoven Christine Van, Vance Jeffery, Vardarajan Badri N, van der Lugt Aad, Dongen Jasper Van, van Rooij Jeroen, van Swieten John, Vandenberghe Rik, Verhey Frans, Vidal Jean-Sébastien, Vogelgsang Jonathan, Vyhnalek Martin, Wagner Michael, Wallon David, Wang Li-San, Wang Ruiqi, Weinhold Leonie, Wiltfang Jens, Windle Gill, Woods Bob, Yannakoulia Mary, Zare Habil, Zhao Yi, Zhang Xiaoling, Zhu Congcong, Zulaica Miren, EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Farrer Lindsay A, Psaty Bruce M, Ghanbari Mohsen, Raj Towfique, Sachdev Perminder, Mather Karen, Jessen Frank, Ikram M Arfan, de Mendonça Alexandre, Hort Jakub, Tsolaki Magda, Pericak-Vance Margaret A, Amouyel Philippe, Williams Julie, Frikke-Schmidt Ruth, Clarimon Jordi, Deleuze Jean-François, Rossi Giacomina, Seshadri Sudha, Andreassen Ole A, Ingelsson Martin, Hiltunen Mikko, Sleegers Kristel, Schellenberg Gerard D, van Duijn Cornelia M, Sims Rebecca, van der Flier Wiesje M, Ruiz Agustín, Ramirez Alfredo, Lambert Jean-Charles

СтатьяПоддержка исследования: вне правительства СШАПоддержка правительства СШАПоддержка NIH: внешняя программаПеревод пока не подготовлен

Аннотация

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.

Для цитирования: Bellenguez Céline, Küçükali Fahri, Jansen Iris E, Kleineidam Luca, Moreno-Grau Sonia, Amin Najaf, Naj Adam C, Campos-Martin Rafael, Grenier-Boley Benjamin, Andrade Victor, Holmans Peter A, Boland Anne, Damotte Vincent, van der Lee Sven J, Costa Marcos R, Kuulasmaa Teemu, Yang Qiong, de Rojas Itziar, Bis Joshua C, Yaqub Amber, Prokic Ivana, Chapuis Julien, Ahmad Shahzad, Giedraitis Vilmantas, Aarsland Dag, Garcia-Gonzalez Pablo, Abdelnour Carla, Alarcón-Martín Emilio, Alcolea Daniel, Alegret Montserrat, Alvarez Ignacio, Álvarez Victoria, Armstrong Nicola J, Tsolaki Anthoula, Antúnez Carmen, Appollonio Ildebrando, Arcaro Marina, Archetti Silvana, Pastor Alfonso Arias, Arosio Beatrice, Athanasiu Lavinia, Bailly Henri, Banaj Nerisa, Baquero Miquel, Barral Sandra, Beiser Alexa, Pastor Ana Belén, Below Jennifer E, Benchek Penelope, Benussi Luisa, Berr Claudine, Besse Céline, Bessi Valentina, Binetti Giuliano, Bizarro Alessandra, Blesa Rafael, Boada Mercè, Boerwinkle Eric, Borroni Barbara, Boschi Silvia, Bossù Paola, Bråthen Geir, Bressler Jan, Bresner Catherine, Brodaty Henry, Brookes Keeley J, Brusco Luis Ignacio, Buiza-Rueda Dolores, Bûrger Katharina, Burholt Vanessa, Bush William S, Calero Miguel, Cantwell Laura B, Chene Geneviève, Chung Jaeyoon, Cuccaro Michael L, Carracedo Ángel, Cecchetti Roberta, Cervera-Carles Laura, Charbonnier Camille, Chen Hung-Hsin, Chillotti Caterina, Ciccone Simona, Claassen Jurgen A H R, Clark Christopher, Conti Elisa, Corma-Gómez Anaïs, Costantini Emanuele, Custodero Carlo, Daian Delphine, Dalmasso Maria Carolina, Daniele Antonio, Dardiotis Efthimios, Dartigues Jean-François, de Deyn Peter Paul, de Paiva Lopes Katia, de Witte Lot D, Debette Stéphanie, Deckert Jürgen, Del Ser Teodoro, Denning Nicola, DeStefano Anita, Dichgans Martin, Diehl-Schmid Janine, Diez-Fairen Mónica, Rossi Paolo Dionigi, Djurovic Srdjan, Duron Emmanuelle, Düzel Emrah, Dufouil Carole, Eiriksdottir Gudny, Engelborghs Sebastiaan, Escott-Price Valentina, Espinosa Ana, Ewers Michael, Faber Kelley M, Fabrizio Tagliavini, Nielsen Sune Fallgaard, Fardo David W, Farotti Lucia, Fenoglio Chiara, Fernández-Fuertes Marta, Ferrari Raffaele, Ferreira Catarina B, Ferri Evelyn, Fin Bertrand, Fischer Peter, Fladby Tormod, Fließbach Klaus, Fongang Bernard, Fornage Myriam, Fortea Juan, Foroud Tatiana M, Fostinelli Silvia, Fox Nick C, Franco-Macías Emlio, Bullido María J, Frank-García Ana, Froelich Lutz, Fulton-Howard Brian, Galimberti Daniela, García-Alberca Jose Maria, García-González Pablo, Garcia-Madrona Sebastian, Garcia-Ribas Guillermo, Ghidoni Roberta, Giegling Ina, Giorgio Giaccone, Goate Alison M, Goldhardt Oliver, Gomez-Fonseca Duber, González-Pérez Antonio, Graff Caroline, Grande Giulia, Green Emma, Grimmer Timo, Grünblatt Edna, Grunin Michelle, Gudnason Vilmundur, Guetta-Baranes Tamar, Haapasalo Annakaisa, Hadjigeorgiou Georgios, Haines Jonathan L, Hamilton-Nelson Kara L, Hampel Harald, Hanon Olivier, Hardy John, Hartmann Annette M, Hausner Lucrezia, Harwood Janet, Heilmann-Heimbach Stefanie, Helisalmi Seppo, Heneka Michael T, Hernández Isabel, Herrmann Martin J, Hoffmann Per, Holmes Clive, Holstege Henne, Vilas Raquel Huerto, Hulsman Marc, Humphrey Jack, Biessels Geert Jan, Jian Xueqiu, Johansson Charlotte, Jun Gyungah R, Kastumata Yuriko, Kauwe John, Kehoe Patrick G, Kilander Lena, Ståhlbom Anne Kinhult, Kivipelto Miia, Koivisto Anne, Kornhuber Johannes, Kosmidis Mary H, Kukull Walter A, Kuksa Pavel P, Kunkle Brian W, Kuzma Amanda B, Lage Carmen, Laukka Erika J, Launer Lenore, Lauria Alessandra, Lee Chien-Yueh, Lehtisalo Jenni, Lerch Ondrej, Lleó Alberto, Longstreth William, Lopez Oscar, de Munain Adolfo Lopez, Love Seth, Löwemark Malin, Luckcuck Lauren, Lunetta Kathryn L, Ma Yiyi, Macías Juan, MacLeod Catherine A, Maier Wolfgang, Mangialasche Francesca, Spallazzi Marco, Marquié Marta, Marshall Rachel, Martin Eden R, Montes Angel Martín, Rodríguez Carmen Martínez, Masullo Carlo, Mayeux Richard, Mead Simon, Mecocci Patrizia, Medina Miguel, Meggy Alun, Mehrabian Shima, Mendoza Silvia, Menéndez-González Manuel, Mir Pablo, Moebus Susanne, Mol Merel, Molina-Porcel Laura, Montrreal Laura, Morelli Laura, Moreno Fermin, Morgan Kevin, Mosley Thomas, Nöthen Markus M, Muchnik Carolina, Mukherjee Shubhabrata, Nacmias Benedetta, Ngandu Tiia, Nicolas Gael, Nordestgaard Børge G, Olaso Robert, Orellana Adelina, Orsini Michela, Ortega Gemma, Padovani Alessandro, Paolo Caffarra, Papenberg Goran, Parnetti Lucilla, Pasquier Florence, Pastor Pau, Peloso Gina, Pérez-Cordón Alba, Pérez-Tur Jordi, Pericard Pierre, Peters Oliver, Pijnenburg Yolande A L, Pineda Juan A, Piñol-Ripoll Gerard, Pisanu Claudia, Polak Thomas, Popp Julius, Posthuma Danielle, Priller Josef, Puerta Raquel, Quenez Olivier, Quintela Inés, Thomassen Jesper Qvist, Rábano Alberto, Rainero Innocenzo, Rajabli Farid, Ramakers Inez, Real Luis M, Reinders Marcel J T, Reitz Christiane, Reyes-Dumeyer Dolly, Ridge Perry, Riedel-Heller Steffi, Riederer Peter, Roberto Natalia, Rodriguez-Rodriguez Eloy, Rongve Arvid, Allende Irene Rosas, Rosende-Roca Maitée, Royo Jose Luis, Rubino Elisa, Rujescu Dan, Sáez María Eugenia, Sakka Paraskevi, Saltvedt Ingvild, Sanabria Ángela, Sánchez-Arjona María Bernal, Sanchez-Garcia Florentino, Juan Pascual Sánchez, Sánchez-Valle Raquel, Sando Sigrid B, Sarnowski Chloé, Satizabal Claudia L, Scamosci Michela, Scarmeas Nikolaos, Scarpini Elio, Scheltens Philip, Scherbaum Norbert, Scherer Martin, Schmid Matthias, Schneider Anja, Schott Jonathan M, Selbæk Geir, Seripa Davide, Serrano Manuel, Sha Jin, Shadrin Alexey A, Skrobot Olivia, Slifer Susan, Snijders Gijsje J L, Soininen Hilkka, Solfrizzi Vincenzo, Solomon Alina, Song Yeunjoo, Sorbi Sandro, Sotolongo-Grau Oscar, Spalletta Gianfranco, Spottke Annika, Squassina Alessio, Stordal Eystein, Tartan Juan Pablo, Tárraga Lluís, Tesí Niccolo, Thalamuthu Anbupalam, Thomas Tegos, Tosto Giuseppe, Traykov Latchezar, Tremolizzo Lucio, Tybjærg-Hansen Anne, Uitterlinden Andre, Ullgren Abbe, Ulstein Ingun, Valero Sergi, Valladares Otto, Broeckhoven Christine Van, Vance Jeffery, Vardarajan Badri N, van der Lugt Aad, Dongen Jasper Van, van Rooij Jeroen, van Swieten John, Vandenberghe Rik, Verhey Frans, Vidal Jean-Sébastien, Vogelgsang Jonathan, Vyhnalek Martin, Wagner Michael, Wallon David, Wang Li-San, Wang Ruiqi, Weinhold Leonie, Wiltfang Jens, Windle Gill, Woods Bob, Yannakoulia Mary, Zare Habil, Zhao Yi, Zhang Xiaoling, Zhu Congcong, Zulaica Miren, EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Farrer Lindsay A, Psaty Bruce M, Ghanbari Mohsen, Raj Towfique, Sachdev Perminder, Mather Karen, Jessen Frank, Ikram M Arfan, de Mendonça Alexandre, Hort Jakub, Tsolaki Magda, Pericak-Vance Margaret A, Amouyel Philippe, Williams Julie, Frikke-Schmidt Ruth, Clarimon Jordi, Deleuze Jean-François, Rossi Giacomina, Seshadri Sudha, Andreassen Ole A, Ingelsson Martin, Hiltunen Mikko, Sleegers Kristel, Schellenberg Gerard D, van Duijn Cornelia M, Sims Rebecca, van der Flier Wiesje M, Ruiz Agustín, Ramirez Alfredo, Lambert Jean-Charles. New insights into the genetic etiology of Alzheimer's disease and related dementias.. Nature genetics. 2022. DOI: 10.1038/s41588-022-01024-z.

Предметные рубрики MeSH

Alzheimer Disease Cognitive Dysfunction Genome-Wide Association Study Humans tau Proteins

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