[en] BACKGROUND: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. PRINCIPAL FINDINGS: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10-6) and 14 (IGHV1-67 p = 7.9x10-8) which indexed novel susceptibility loci. SIGNIFICANCE: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Disciplines :
Genetics & genetic processes
Author, co-author :
Escott-Price, Valentina
Bellenguez, Celine
Wang, Li-San
Choi, Seung-Hoan
Harold, Denise
Jones, Lesley
Holmans, Peter
Gerrish, Amy
Vedernikov, Alexey
Richards, Alexander
DeStefano, Anita L.
Lambert, Jean-Charles
Ibrahim-Verbaas, Carla A.
Naj, Adam C.
Sims, Rebecca
Jun, Gyungah
Bis, Joshua C.
Beecham, Gary W.
Grenier-Boley, Benjamin
Russo, Giancarlo
Thornton-Wells, Tricia A.
Denning, Nicola
Smith, Albert V.
Chouraki, Vincent
Thomas, Charlene
Ikram, M. Arfan
Zelenika, Diana
Vardarajan, Badri N.
Kamatani, Yoichiro
Lin, Chiao-Feng
Schmidt, Helena
Kunkle, Brian
Dunstan, Melanie L.
Vronskaya, Maria
Johnson, Andrew D.
Ruiz, Agustin
Bihoreau, Marie-Therese
Reitz, Christiane
Pasquier, Florence
Hollingworth, Paul
Hanon, Olivier
Fitzpatrick, Annette L.
Buxbaum, Joseph D.
Campion, Dominique
Crane, Paul K.
Baldwin, Clinton
Becker, Tim
Gudnason, Vilmundur
Cruchaga, Carlos
Craig, David
Amin, Najaf
Berr, Claudine
Lopez, Oscar L.
De Jager, Philip L.
Deramecourt, Vincent
Johnston, Janet A.
Evans, Denis
Lovestone, Simon
Letenneur, Luc
Hernandez, Isabel
Rubinsztein, David C.
Eiriksdottir, Gudny
Sleegers, Kristel
Goate, Alison M.
Fievet, Nathalie
Huentelman, Matthew J.
Gill, Michael
Brown, Kristelle
Kamboh, M. Ilyas
Keller, Lina
Barberger-Gateau, Pascale
McGuinness, Bernadette
Larson, Eric B.
Myers, Amanda J.
Dufouil, Carole
Todd, Stephen
Wallon, David
Love, Seth
Rogaeva, Ekaterina
Gallacher, John
George-Hyslop, Peter St
Clarimon, Jordi
Lleo, Alberto
Bayer, Anthony
Tsuang, Debby W.
Yu, Lei
Tsolaki, Magda
Bossu, Paola
Spalletta, Gianfranco
Proitsi, Petra
Collinge, John
Sorbi, Sandro
Garcia, Florentino Sanchez
Fox, Nick C.
Hardy, John
Naranjo, Maria Candida Deniz
Bosco, Paolo
Clarke, Robert
Brayne, Carol
Galimberti, Daniela
Scarpini, Elio
Bonuccelli, Ubaldo
Mancuso, Michelangelo
Siciliano, Gabriele
Moebus, Susanne
Mecocci, Patrizia
Zompo, Maria Del
Maier, Wolfgang
Hampel, Harald
Pilotto, Alberto
Frank-Garcia, Ana
Panza, Francesco
Solfrizzi, Vincenzo
Caffarra, Paolo
Nacmias, Benedetta
Perry, William
Mayhaus, Manuel
Lannfelt, Lars
Hakonarson, Hakon
Pichler, Sabrina
Carrasquillo, Minerva M.
Ingelsson, Martin
Beekly, Duane
Alvarez, Victoria
Zou, Fanggeng
Valladares, Otto
Younkin, Steven G.
Coto, Eliecer
Hamilton-Nelson, Kara L.
GU, Wei ; University Hospital, Saarland, Germany, > Department of Psychiatry
