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Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

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

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Citation
PLoS ONE 2014, 9 (6):e94661
Abstract
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.
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.
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.
Description
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.
Additional Links
http://dx.doi.org/10.1371/journal.pone.0094661
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055488/
Rights
openAccess
openAccess
ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0094661
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