Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
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阿尔茨海默病的常见变异和多基因风险评分的风险分层。
DOI:
10.1038/s41467-021-22491-8
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发表时间:
2021-06-07
影响因子:
16.6
通讯作者:
Ruiz A
中科院分区:
文献类型:
--
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
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. Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.
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DOI:
10.1056/nejmoa1211851
发表时间:
2013-01-10
期刊:
The New England journal of medicine
影响因子:
--
作者:
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者:
Alzheimer Genetic Analysis Group
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:
14
作者:
通讯作者:
--
DOI:
10.1056/nejmoa1706441
发表时间:
2018-05-03
期刊:
The New England journal of medicine
影响因子:
--
作者:
Egan MF;Kost J;Tariot PN;Aisen PS;Cummings JL;Vellas B;Sur C;Mukai Y;Voss T;Furtek C;Mahoney E;Harper Mozley L;Vandenberghe R;Mo Y;Michelson D
通讯作者:
Michelson D
DOI:
10.3233/jad-170049
发表时间:
2017
期刊:
Journal of Alzheimer's disease : JAD
影响因子:
--
作者:
Myrum C;Nikolaienko O;Bramham CR;Haavik J;Zayats T
通讯作者:
Zayats T