New insights into the genetic etiology of Alzheimer's disease and related dementias.
New insights into the genetic etiology of Alzheimer's disease and related dementias.
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DOI：
10.1038/s41588-022-01024-z
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发表时间：
2022-04
期刊：
影响因子：
30.8
通讯作者：
Lambert, Jean-Charles
中科院分区：
文献类型：
--
作者：
Bellenguez, Celine;Kucukali, 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;Alarcon-Martin, Emilio;Alcolea, Daniel;Alegret, Montserrat;Alvarez, Ignacio;Alvarez, Victoria;Armstrong, Nicola J.;Tsolaki, Anthoula;Antunez, Carmen;Appollonio, Ildebrando;Arcaro, Marina;Archetti, Silvana;Arias Pastor, Alfonso;Arosio, Beatrice;Athanasiu, Lavinia;Bailly, Henri;Banaj, Nerisa;Baquero, Miquel;Barral, Sandra;Beiser, Alexa;Pastor, Ana Belen;Below, Jennifer E.;Benchek, Penelope;Benussi, Luisa;Berr, Claudine;Besse, Celine;Bessi, Valentina;Binetti, Giuliano;Bizarro, Alessandra;Blesa, Rafael;Boada, Merce;Boerwinkle, Eric;Borroni, Barbara;Boschi, Silvia;Bossu, Paola;Brathen, Geir;Bressler, Jan;Bresner, Catherine;Brodaty, Henry;Brookes, Keeley J.;Ignacio Brusco, Luis;Buiza-Rueda, Dolores;Burger, Katharina;Burholt, Vanessa;Bush, William S.;Calero, Miguel;Cantwell, Laura B.;Chene, Genevieve;Chung, Jaeyoon;Cuccaro, Michael L.;Cecchetti, Roberta;Cervera-Carles, Laura;Charbonnier, Camille;Chen, Hung-Hsin;Chillotti, Caterina;Ciccone, Simona;Claassen, Jurgen A. H. R.;Clark, Christopher;Conti, Elisa;Corma-Gomez, Anais;Costantini, Emanuele;Custodero, Carlo;Daian, Delphine;Dalmasso, Maria Carolina;Daniele, Antonio;Dardiotis, Efthimios;Dartigues, Jean-Francois;de Deyn, Peter Paul;Lopes, Katia de Paiva;De Witte, Lot D.;Debette, Stephanie;Deckert, Jurgen;del Ser, Teodoro;Denning, Nicola;Destefano, Anita;Dichgans, Martin;Diehl-Schmid, Janine;Diez-Fairen, Monica;Rossi, Paolo Dionigi;Djurovic, Srdjan;Duron, Emmanuelle;Duzel, 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;Fernandez-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-Macias, Emlio;Bullido, Maria J.;Frank-Garcia, Ana;Froelich, Lutz;Fulton-Howard, Brian;Galimberti, Daniela;Maria Garcia-Alberca, Jose;Garcia-Madrona, Sebastian;Garcia-Ribas, Guillermo;Ghidoni, Roberta;Giegling, Ina;Giorgio, Giaccone;Goate, Alison M.;Goldhardt, Oliver;Gomez-Fonseca, Duber;Gonzalez-Perez, Antonio;Graff, Caroline;Grande, Giulia;Green, Emma;Grimmer, Timo;Grunblatt, 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.;Hernandez, Isabel;Herrmann, Martin J.;Hoffmann, Per;Holmes, Clive;Holstege, Henne;Huerto Vilas, Raquel;Hulsman, Marc;Humphrey, Jack;Biessels, Geert Jan;Jian, Xueqiu;Johansson, Charlotte;Jun, Gyungah R.;Kastumata, Yuriko;Kauwe, John;Kehoe, Patrick G.;Kilander, Lena;Stahlbom, 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;Lleo, Alberto;Longstreth, William, Jr.;Lopez, Oscar;Lopez de Munain, Adolfo;Love, Seth;Lowemark, Malin;Luckcuck, Lauren;Lunetta, Kathryn L.;Ma, Yiyi;Macias, Juan;Macleod, Catherine A.;Maier, Wolfgang;Mangialasche, Francesca;Spallazzi, Marco;Marquie, Marta;Marshall, Rachel;Martin, Eden R.;Martin Montes, Angel;Martinez Rodriguez, Carmen;Masullo, Carlo;Mayeux, Richard;Mead, Simon;Mecocci, Patrizia;Medina, Miguel;Meggy, Alun;Mehrabian, Shima;Mendoza, Silvia;Menendez-Gonzalez, Manuel;Mir, Pablo;Moebus, Susanne;Mol, Merel;Molina-Porcel, Laura;Montrreal, Laura;Morelli, Laura;Moreno, Fermin;Morgan, Kevin;Mosley, Thomas;Nothen, Markus M.;Muchnik, Carolina;Mukherjee, Shubhabrata;Nacmias, Benedetta;Ngandu, Tiia;Nicolas, Gael;Nordestgaard, Borge G.;Olaso, Robert;Orellana, Adelina;Orsini, Michela;Ortega, Gemma;Padovani, Alessandro;Paolo, Caffarra;Papenberg, Goran;Parnetti, Lucilla;Pasquier, Florence;Pastor, Pau;Peloso, Gina;Perez-Cordon, Alba;Perez-Tur, Jordi;Pericard, Pierre;Peters, Oliver;Pijnenburg, Yolande A. L.;Pineda, Juan A.;Pinol-Ripoll, Gerard;Pisanu, Laudia;Polak, Thomas;Popp, Julius;Posthuma, Danielle;Priller, Josef;Puerta, Raquel;Quenez, Olivier;Quintela, Ines;Thomassen, Jesper Qvist;Rabano, 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;Rosas Allende, Irene;Rosende-Roca, Maitee;Luis Royo, Jose;Rubino, Elisa;Rujescu, Dan;Eugenia Saez, Maria;Sakka, Paraskevi;Saltvedt, Ingvild;Bernal Sanchez-Arjona, Maria;Sanchez-Garcia, Florentino;Sanchez Juan, Pascual;Sanchez-Valle, Raquel;Sando, Sigrid B.;Sarnowski, Chloe;Satizabal, Claudia L.;Scamosci, Michela;Scarmeas, Nikolaos;Scarpini, Elio;Scheltens, Philip;Scherbaum, Norbert;Scherer, Martin;Schmid, Matthias;Schneider, Anja;Schott, Jonathan M.;Selbaek, 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;Pablo Tartan, Juan;Tarraga, Lluis;Tesi, Niccolo;Thalamuthu, Anbupalam;Thomas, Tegos;Tosto, Giuseppe;Traykov, Latchezar;Tremolizzo, Lucio;Tybjaerg-Hansen, Anne;Uitterlinden, Andre;Ullgren, Abbe;Ulstein, Ingun;Valero, Sergi;Valladares, Otto;Van Broeckhoven, Christine;Vance, Jeffery;Vardarajan, Badri N.;van der Lugt, Aad;Van Dongen, Jasper;van Rooij, Jeroen;van Swieten, John;Vandenberghe, Rik;Verhey, Frans;Vidal, Jean-Sebastien;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;Farrer, Lindsay A.;Psaty, Bruce M.;Ghanbari, Mohsen;Raj, Towfique;Sachdev, Perminder;Mather, Karen;Jessen, Frank;Ikram, M. Arfan;de Mendonca, Alexandre;Hort, Jakub;Tsolaki, Magda;Pericak-Vance, Margaret A.;Amouyel, Philippe;Williams, Julie;Frikke-Schmidt, Ruth;Clarimon, Jordi;Deleuze, Jean-Francois;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, Agustin;Ramirez, Alfredo;Lambert, Jean-Charles
描述阿尔茨海默病(AD)和相关痴呆(ADD)的遗传格局为更好地了解相关的病理生理过程提供了独特的机会。我们进行了一项分两个阶段的全基因组关联研究，共111,326例临床诊断/替代的AD病例和677,663名对照。我们发现了75个风险基因座，其中42个在分析时是新的。途径富集化分析证实了淀粉样蛋白/tau途径的参与，并强调了小胶质细胞的影响。新基因座的基因优先顺序确定了31个基因，这些基因暗示了新的遗传相关过程，包括通过线性泛素链组装复合体的肿瘤坏死因子α途径。我们还建立了一个新的遗传风险评分，与未来AD/痴呆的风险或从轻度认知障碍到AD/痴呆的进展相关。除了年龄和载脂蛋白Eε4等位基因的影响外，预测的改进还导致AD风险从最低到最高增加1.6%到1.9%。对阿尔茨海默病和相关痴呆症的全基因组关联研究的荟萃分析确定了新的基因位点，并能够生成与未来阿尔茨海默病和痴呆症的风险相关的新的遗传风险分数。
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. Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.
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DOI：
10.3233/jad-150749
发表时间：
2016-06-18
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Chouraki V;Reitz C;Maury F;Bis JC;Bellenguez C;Yu L;Jakobsdottir J;Mukherjee S;Adams HH;Choi SH;Larson EB;Fitzpatrick A;Uitterlinden AG;de Jager PL;Hofman A;Gudnason V;Vardarajan B;Ibrahim-Verbaas C;van der Lee SJ;Lopez O;Dartigues JF;Berr C;Amouyel P;Bennett DA;van Duijn C;DeStefano AL;Launer LJ;Ikram MA;Crane PK;Lambert JC;Mayeux R;Seshadri S;International Genomics of Alzheimer’s Project
通讯作者：
International Genomics of Alzheimer’s Project
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
16.6
作者：
de Rojas I;Moreno-Grau S;Tesi N;Grenier-Boley B;Andrade V;Jansen IE;Pedersen NL;Stringa N;Zettergren A;Hernández I;Montrreal L;Antúnez C;Antonell A;Tankard RM;Bis JC;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 JL;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 AC;Lemstra AW;Benaque A;Pérez-Cordón A;Benussi A;Rábano A;Padovani A;Squassina A;de Mendonça A;Arias Pastor A;Kok AAL;Meggy A;Pastor AB;Espinosa A;Corma-Gómez A;Martín Montes A;Sanabria Á;DeStefano AL;Schneider A;Haapasalo A;Kinhult Ståhlbom A;Tybjærg-Hansen A;Hartmann AM;Spottke A;Corbatón-Anchuelo A;Rongve A;Borroni B;Arosio B;Nacmias B;Nordestgaard BG;Kunkle BW;Charbonnier C;Abdelnour C;Masullo C;Martínez Rodríguez C;Muñoz-Fernandez C;Dufouil C;Graff C;Ferreira CB;Chillotti C;Reynolds CA;Fenoglio C;Van Broeckhoven C;Clark C;Pisanu C;Satizabal CL;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 IK;Alvarez I;Appollonio I;Giegling I;Skoog I;Saltvedt I;Rainero I;Rosas Allende I;Hort J;Diehl-Schmid J;Van Dongen J;Vidal JS;Lehtisalo J;Wiltfang J;Thomassen JQ;Kornhuber J;Haines JL;Vogelgsang J;Pineda JA;Fortea J;Popp J;Deckert J;Buerger K;Morgan K;Fließbach K;Sleegers K;Molina-Porcel L;Kilander L;Weinhold L;Farrer LA;Wang LS;Kleineidam L;Farotti L;Parnetti L;Tremolizzo L;Hausner L;Benussi L;Froelich L;Ikram MA;Deniz-Naranjo MC;Tsolaki M;Rosende-Roca M;Löwenmark M;Hulsman M;Spallazzi M;Pericak-Vance MA;Esiri M;Bernal Sánchez-Arjona M;Dalmasso MC;Martínez-Larrad MT;Arcaro M;Nöthen MM;Fernández-Fuertes M;Dichgans M;Ingelsson M;Herrmann MJ;Scherer M;Vyhnalek M;Kosmidis MH;Yannakoulia M;Schmid M;Ewers M;Heneka MT;Wagner M;Scamosci M;Kivipelto M;Hiltunen M;Zulaica M;Alegret M;Fornage M;Roberto N;van Schoor NM;Seidu NM;Banaj N;Armstrong NJ;Scarmeas N;Scherbaum N;Goldhardt O;Hanon O;Peters O;Skrobot OA;Quenez O;Lerch O;Bossù P;Caffarra P;Dionigi Rossi P;Sakka P;Mecocci P;Hoffmann P;Holmans PA;Fischer P;Riederer P;Yang Q;Marshall R;Kalaria RN;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 YAL;EADB contributors;GR@ACE study group;DEGESCO consortium;IGAP (ADGC, CHARGE, EADI, GERAD);PGC-ALZ consortia;Kehoe PG;Garcia-Ribas G;Sánchez-Juan P;Pastor P;Pérez-Tur J;Piñol-Ripoll G;Lopez de Munain A;García-Alberca JM;Bullido MJ;Álvarez V;Lleó A;Real LM;Mir P;Medina M;Scheltens P;Holstege H;Marquié M;Sáez ME;Carracedo Á;Amouyel P;Schellenberg GD;Williams J;Seshadri S;van Duijn CM;Mather KA;Sánchez-Valle R;Serrano-Ríos M;Orellana A;Tárraga L;Blennow K;Huisman M;Andreassen OA;Posthuma D;Clarimón J;Boada M;van der Flier WM;Ramirez A;Lambert JC;van der Lee SJ;Ruiz A
通讯作者：
Ruiz A
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
12.7
作者：
Chapuis J;Flaig A;Grenier-Boley B;Eysert F;Pottiez V;Deloison G;Vandeputte A;Ayral AM;Mendes T;Desai S;Goate AM;Kauwe JSK;Leroux F;Herledan A;Demiautte F;Bauer C;Checler F;Petersen RC;Blennow K;Zetterberg H;Minthon L;Van Deerlin VM;Lee VM;Shaw LM;Trojanowski JQ;Albert M;Moghekar A;O'Brien R;Peskind ER;Malmanche N;Schellenberg GD;Dourlen P;Song OR;Cruchaga C;Amouyel P;Deprez B;Brodin P;Lambert JC;ADGC, Alzheimer’s Disease Neuroimaging Initiative
通讯作者：
ADGC, Alzheimer’s Disease Neuroimaging Initiative