Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
Creators: name: Escott-Price, Valentina
name: Bellenguez, Céline
name: Wang, Li-San
name: Choi, Seung-Hoan
name: Harold, Denise
name: Jones, Lesley
name: Gerrish, Amy
name: Holmans, Peter
name: Vedernikov, Alexey
name: Richards, Alexander
name: DeStefano, Anita L.
name: Lambert, Jean-Charles
name: Ibrahim-Verbaas, Carla A.
name: Naj, Adam C.
name: Sims, Rebecca
name: Jun, Gyungah
name: Bis, Joshua C.
name: Beecham, Gary W.
name: Grenier-Boley, Benjamin
name: Russo, Giancarlo
name: Thornton-Wells, Tricia A.
name: Denning, Nicola
name: Smith, Albert V.
name: Chouraki, Vincent
name: Thomas, Charlene
name: Ikram, M. Arfan
name: Zelenika, Diana
name: Vardarajan, Badri N.
name: Kamatani, Yoichiro
name: Lin, Chiao-Feng
name: Schmidt, Helena
name: Kunkle, Brian
name: Dunstan, Melanie L.
name: Vronskaya, Maria
name: Johnson, Andrew D.
name: Ruiz, Agustin
name: Bihoreau, Marie-Thérèse
name: Reitz, Christiane
name: Pasquier, Florence
name: Hollingworth, Paul
name: Hanon, Olivier
name: Fitzpatrick, Annette L.
name: Buxbaum, Joseph D.
name: Campion, Dominique
name: Crane, Paul K.
name: Baldwin, Clinton
name: Becker, Tim
name: Gudnason, Vilmundur
name: Cruchaga, Carlos
name: Craig, David
name: Amin, Najaf
name: Berr, Claudine
name: Lopez, Oscar L.
name: De Jager, Philip Lawrence
name: Deramecourt, Vincent
name: Johnston, Janet A.
name: Evans, Denis
name: Lovestone, Simon
name: Letenneur, Luc
name: Hernández, Isabel
name: Rubinsztein, David C.
name: Eiriksdottir, Gudny
name: Goate, Alison M.
name: Sleegers, Kristel
name: Fiévet, Nathalie
name: Huentelman, Matthew J.
name: Gill, Michael
name: Brown, Kristelle
name: Kamboh, M. Ilyas
name: Keller, Lina
name: Barberger-Gateau, Pascale
name: McGuinness, Bernadette
name: Larson, Eric B.
name: Myers, Amanda J.
name: Dufouil, Carole
name: Todd, Stephen
name: Wallon, David
name: Love, Seth
name: Rogaeva, Ekaterina
name: Gallacher, John
name: St George-Hyslop, Peter
name: Clarimon, Jordi
name: Lleo, Alberto
name: Bayer, Anthony
name: Tsuang, Debby W.
name: Yu, Lei
name: Tsolaki, Magda
name: Bossù, Paola
name: Spalletta, Gianfranco
name: Proitsi, Petra
name: Collinge, John
name: Sorbi, Sandro
name: Sanchez Garcia, Florentino
name: Fox, Nick C.
name: Hardy, John
name: Naranjo, Maria Candida Deniz
name: Bosco, Paolo
name: Clarke, Robert
name: Brayne, Carol
name: Galimberti, Daniela
name: Scarpini, Elio
name: Bonuccelli, Ubaldo
name: Mancuso, Michelangelo
name: Siciliano, Gabriele
name: Moebus, Susanne
name: Mecocci, Patrizia
name: Del Zompo, Maria
name: Maier, Wolfgang
name: Hampel, Harald
name: Pilotto, Alberto
name: Frank-García, Ana
name: Panza, Francesco
name: Solfrizzi, Vincenzo
name: Caffarra, Paolo
name: Nacmias, Benedetta
name: Perry, William
name: Mayhaus, Manuel
name: Lannfelt, Lars
name: Hakonarson, Hakon
name: Pichler, Sabrina
name: Carrasquillo, Minerva M.
name: Ingelsson, Martin
name: Beekly, Duane
name: Alvarez, Victoria
name: Zou, Fanggeng
name: Valladares, Otto
name: Younkin, Steven G.
name: Coto, Eliecer
name: Hamilton-Nelson, Kara L.
name: Gu, Wei
name: Razquin, Cristina
name: Pastor, Pau
name: Mateo, Ignacio
name: Owen, Michael J.
name: Faber, Kelley M.
name: Jonsson, Palmi V.
name: Combarros, Onofre
name: O'Donovan, Michael C.
name: Cantwell, Laura B.
name: Soininen, Hilkka
name: Blacker, Deborah
name: Mead, Simon
name: Mosley Jr., Thomas H.
name: Bennett, David A.
name: Harris, Tamara B.
name: Fratiglioni, Laura
name: Holmes, Clive
name: De Bruijn, Renee F. A. G.
name: Passmore, Peter
name: Montine, Thomas J.
name: Bettens, Karolien
name: Rotter, Jerome I.
name: Brice, Alexis
name: Morgan, Kevin
name: Foroud, Tatiana M.
name: Kukull, Walter A.
name: Hannequin, Didier
name: Powell, John F.
name: Nalls, Michael A.
name: Ritchie, Karen
name: Lunetta, Kathryn L.
name: Kauwe, John S. K.
name: Boerwinkle, Eric
name: Riemenschneider, Matthias
name: Boada, Mercè
name: Hiltunen, Mikko
name: Martin, Eden R.
name: Schmidt, Reinhold
name: Rujescu, Dan
name: Dartigues, Jean-François
name: Mayeux, Richard Paul
name: Tzourio, Christophe
name: Hofman, Albert
name: Nöthen, Markus M.
name: Graff, Caroline
name: Psaty, Bruce M.
name: Haines, Jonathan L.
name: Lathrop, Mark
name: Pericak-Vance, Margaret A.
name: Launer, Lenore J.
name: Van Broeckhoven, Christine
name: Farrer, Lindsay A.
name: Van Duijn, Cornelia M.
name: Ramirez, Alfredo
name: Seshadri, Sudha
name: Schellenberg, Gerard D.
name: Amouyel, Philippe
name: Williams, Julie
name: United Kingdom Brain Expression Consortium
Publisher: name: Columbia University
Year: 2014
Subjects: subject: Disease susceptibility--Genetic aspects
subject: Genomics--Data processing
subject: Alzheimer's disease--Genetic aspects
subject: Medical sciences
subject: Pathology
subject: Genetics
subject: FOS: Biological sciences

description: 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 = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) 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.