Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | e94661 |
| Journal | PloS one |
| Volume | 9 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 12 2014 |
ASJC Scopus subject areas
- General
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Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. / 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.; 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; Arfan Ikram, M.; 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 Thérèse; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Hanon, Olivier; Fitzpatrick, Annette L.; Buxbaum, Joseph D.; Campion, Dominique; Crane, Paul K.; Becker, Clinton Baldwin 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; Hernández, Isabel; Rubinsztein, David C.; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M.; Fiévet, 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; St George-Hyslop, Peter; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W.; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petra; Collinge, John; Sorbi, Sandro; Sanchez Garcia, Florentino; 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; Del Zompo, Maria; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Frank-García, 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; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J.; Faber, Kelley M.; Jonsson, Palmi V.; Combarros, Onofre; O'Donovan, Michael C.; Cantwell, Laura B.; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H.; Bennett, David A.; Harris, Tamara B.; Fratiglioni, Laura; Holmes, Clive; De Bruijn, Renee F.A.G.; Passmore, Peter; Montine, Thomas J.; Bettens, Karolien; Rotter, Jerome I.; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M.; Kukull, Walter A.; Hannequin, Didier; Powell, John F.; Nalls, Michael A.; Ritchie, Karen; Lunetta, Kathryn L.; Kauwe, John S.K.; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R.; Schmidt, Reinhold; Rujescu, Dan; Dartigues, Jean François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M.; Graff, Caroline; Psaty, Bruce M.; Haines, Jonathan L.; Lathrop, Mark; Pericak-Vance, Margaret A.; Launer, Lenore J.; Van Broeckhoven, Christine; Farrer, Lindsay A.; Van Duijn, Cornelia M.; Ramirez, Alfredo; Seshadri, Sudha; Schellenberg, Gerard D.; Amouyel, Philippe; Williams, Julie.
In: PloS one, Vol. 9, No. 6, e94661, 12.06.2014.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease
AU - Escott-Price, Valentina
AU - Bellenguez, Céline
AU - Wang, Li San
AU - Choi, Seung Hoan
AU - Harold, Denise
AU - Jones, Lesley
AU - Holmans, Peter
AU - Gerrish, Amy
AU - Vedernikov, Alexey
AU - Richards, Alexander
AU - DeStefano, Anita L.
AU - Lambert, Jean Charles
AU - Ibrahim-Verbaas, Carla A.
AU - Naj, Adam C.
AU - Sims, Rebecca
AU - Jun, Gyungah
AU - Bis, Joshua C.
AU - Beecham, Gary W.
AU - Grenier-Boley, Benjamin
AU - Russo, Giancarlo
AU - Thornton-Wells, Tricia A.
AU - Denning, Nicola
AU - Smith, Albert V.
AU - Chouraki, Vincent
AU - Thomas, Charlene
AU - Arfan Ikram, M.
AU - Zelenika, Diana
AU - Vardarajan, Badri N.
AU - Kamatani, Yoichiro
AU - Lin, Chiao Feng
AU - Schmidt, Helena
AU - Kunkle, Brian
AU - Dunstan, Melanie L.
AU - Vronskaya, Maria
AU - Johnson, Andrew D.
AU - Ruiz, Agustin
AU - Bihoreau, Marie Thérèse
AU - Reitz, Christiane
AU - Pasquier, Florence
AU - Hollingworth, Paul
AU - Hanon, Olivier
AU - Fitzpatrick, Annette L.
AU - Buxbaum, Joseph D.
AU - Campion, Dominique
AU - Crane, Paul K.
AU - Becker, Clinton Baldwin Tim
AU - Gudnason, Vilmundur
AU - Cruchaga, Carlos
AU - Craig, David
AU - Amin, Najaf
AU - Berr, Claudine
AU - Lopez, Oscar L.
AU - De Jager, Philip L.
AU - Deramecourt, Vincent
AU - Johnston, Janet A.
AU - Evans, Denis
AU - Lovestone, Simon
AU - Letenneur, Luc
AU - Hernández, Isabel
AU - Rubinsztein, David C.
AU - Eiriksdottir, Gudny
AU - Sleegers, Kristel
AU - Goate, Alison M.
AU - Fiévet, Nathalie
AU - Huentelman, Matthew J.
AU - Gill, Michael
AU - Brown, Kristelle
AU - Kamboh, M. Ilyas
AU - Keller, Lina
AU - Barberger-Gateau, Pascale
AU - McGuinness, Bernadette
AU - Larson, Eric B.
AU - Myers, Amanda J.
AU - Dufouil, Carole
AU - Todd, Stephen
AU - Wallon, David
AU - Love, Seth
AU - Rogaeva, Ekaterina
AU - Gallacher, John
AU - St George-Hyslop, Peter
AU - Clarimon, Jordi
AU - Lleo, Alberto
AU - Bayer, Anthony
AU - Tsuang, Debby W.
AU - Yu, Lei
AU - Tsolaki, Magda
AU - Bossù, Paola
AU - Spalletta, Gianfranco
AU - Proitsi, Petra
AU - Collinge, John
AU - Sorbi, Sandro
AU - Sanchez Garcia, Florentino
AU - Fox, Nick C.
AU - Hardy, John
AU - Naranjo, Maria Candida Deniz
AU - Bosco, Paolo
AU - Clarke, Robert
AU - Brayne, Carol
AU - Galimberti, Daniela
AU - Scarpini, Elio
AU - Bonuccelli, Ubaldo
AU - Mancuso, Michelangelo
AU - Siciliano, Gabriele
AU - Moebus, Susanne
AU - Mecocci, Patrizia
AU - Del Zompo, Maria
AU - Maier, Wolfgang
AU - Hampel, Harald
AU - Pilotto, Alberto
AU - Frank-García, Ana
AU - Panza, Francesco
AU - Solfrizzi, Vincenzo
AU - Caffarra, Paolo
AU - Nacmias, Benedetta
AU - Perry, William
AU - Mayhaus, Manuel
AU - Lannfelt, Lars
AU - Hakonarson, Hakon
AU - Pichler, Sabrina
AU - Carrasquillo, Minerva M.
AU - Ingelsson, Martin
AU - Beekly, Duane
AU - Alvarez, Victoria
AU - Zou, Fanggeng
AU - Valladares, Otto
AU - Younkin, Steven G.
AU - Coto, Eliecer
AU - Hamilton-Nelson, Kara L.
AU - Gu, Wei
AU - Razquin, Cristina
AU - Pastor, Pau
AU - Mateo, Ignacio
AU - Owen, Michael J.
AU - Faber, Kelley M.
AU - Jonsson, Palmi V.
AU - Combarros, Onofre
AU - O'Donovan, Michael C.
AU - Cantwell, Laura B.
AU - Soininen, Hilkka
AU - Blacker, Deborah
AU - Mead, Simon
AU - Mosley, Thomas H.
AU - Bennett, David A.
AU - Harris, Tamara B.
AU - Fratiglioni, Laura
AU - Holmes, Clive
AU - De Bruijn, Renee F.A.G.
AU - Passmore, Peter
AU - Montine, Thomas J.
AU - Bettens, Karolien
AU - Rotter, Jerome I.
AU - Brice, Alexis
AU - Morgan, Kevin
AU - Foroud, Tatiana M.
AU - Kukull, Walter A.
AU - Hannequin, Didier
AU - Powell, John F.
AU - Nalls, Michael A.
AU - Ritchie, Karen
AU - Lunetta, Kathryn L.
AU - Kauwe, John S.K.
AU - Boerwinkle, Eric
AU - Riemenschneider, Matthias
AU - Boada, Mercè
AU - Hiltunen, Mikko
AU - Martin, Eden R.
AU - Schmidt, Reinhold
AU - Rujescu, Dan
AU - Dartigues, Jean François
AU - Mayeux, Richard
AU - Tzourio, Christophe
AU - Hofman, Albert
AU - Nöthen, Markus M.
AU - Graff, Caroline
AU - Psaty, Bruce M.
AU - Haines, Jonathan L.
AU - Lathrop, Mark
AU - Pericak-Vance, Margaret A.
AU - Launer, Lenore J.
AU - Van Broeckhoven, Christine
AU - Farrer, Lindsay A.
AU - Van Duijn, Cornelia M.
AU - Ramirez, Alfredo
AU - Seshadri, Sudha
AU - Schellenberg, Gerard D.
AU - Amouyel, Philippe
AU - Williams, Julie
PY - 2014/6/12
Y1 - 2014/6/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84903520463&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903520463&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0094661
DO - 10.1371/journal.pone.0094661
M3 - Article
C2 - 24922517
AN - SCOPUS:84903520463
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e94661
ER -