Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes.
Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes.
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DOI：
10.1186/s13073-022-01070-6
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发表时间：
2022-06-28
期刊：
影响因子：
12.3
通讯作者：
中科院分区：
文献类型：
--
作者：
Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE-ε4, make such estimations difficult. We proposed to estimate the age-related penetrance of SORL1-LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1-LoF variants, stratified by APOE-ε4, derived from the Rotterdam study (N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1-LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE-ε4-stratified SORL1-LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. SORL1-LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE-ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1-LoF variant carriers in case-control study data. We conclude that SORL1-LoF variants should be interpreted in light of APOE genotypes for future clinical applications. The online version contains supplementary material available at 10.1186/s13073-022-01070-6.
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影响因子：
30.8
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
通讯作者：
Lambert, Jean-Charles
DOI：
10.1016/j.jalz.2011.03.005
发表时间：
2011-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
McKhann GM;Knopman DS;Chertkow H;Hyman BT;Jack CR Jr;Kawas CH;Klunk WE;Koroshetz WJ;Manly JJ;Mayeux R;Mohs RC;Morris JC;Rossor MN;Scheltens P;Carrillo MC;Thies B;Weintraub S;Phelps CH
通讯作者：
Phelps CH
影响因子：
7
作者：
Ng, PC;Henikoff, S
通讯作者：
Henikoff, S
影响因子：
11
作者：
Bis JC;Jian X;Kunkle BW;Chen Y;Hamilton-Nelson KL;Bush WS;Salerno WJ;Lancour D;Ma Y;Renton AE;Marcora E;Farrell JJ;Zhao Y;Qu L;Ahmad S;Amin N;Amouyel P;Beecham GW;Below JE;Campion D;Cantwell L;Charbonnier C;Chung J;Crane PK;Cruchaga C;Cupples LA;Dartigues JF;Debette S;Deleuze JF;Fulton L;Gabriel SB;Genin E;Gibbs RA;Goate A;Grenier-Boley B;Gupta N;Haines JL;Havulinna AS;Helisalmi S;Hiltunen M;Howrigan DP;Ikram MA;Kaprio J;Konrad J;Kuzma A;Lander ES;Lathrop M;Lehtimäki T;Lin H;Mattila K;Mayeux R;Muzny DM;Nasser W;Neale B;Nho K;Nicolas G;Patel D;Pericak-Vance MA;Perola M;Psaty BM;Quenez O;Rajabli F;Redon R;Reitz C;Remes AM;Salomaa V;Sarnowski C;Schmidt H;Schmidt M;Schmidt R;Soininen H;Thornton TA;Tosto G;Tzourio C;van der Lee SJ;van Duijn CM;Valladares O;Vardarajan B;Wang LS;Wang W;Wijsman E;Wilson RK;Witten D;Worley KC;Zhang X;Alzheimer’s Disease Sequencing Project;Bellenguez C;Lambert JC;Kurki MI;Palotie A;Daly M;Boerwinkle E;Lunetta KL;Destefano AL;Dupuis J;Martin ER;Schellenberg GD;Seshadri S;Naj AC;Fornage M;Farrer LA
通讯作者：
Farrer LA
DOI：
10.1073/pnas.0503689102
发表时间：
2005-09-20
影响因子：
11.1
作者：
Andersen, OM;Reiche, J;Willnow, TE
通讯作者：
Willnow, TE