Convergent genetic and expression data implicate immunity in Alzheimer's disease.

Jones, L; Lambert, JC; Wang, LS; Choi, SH; Harold, D; Vedernikov, A; Escott-Price, V; Stone, T; Richards, A; Bellenguez,; Ibrahim-Verbaas, CA; Naj, AC; Sims, R; Gerrish, A; Jun, G; DeStefano, AL; Bis, JC; Beecham, GW; Grenier-Boley, B; Russo, G; Thornton-Wells TA; Jones, N; Smith, AV; Chouraki, V; Thomas, C; Ikram, MA; Zelenika, D; Vardarajan, BN; Kamatani, Y; Lin, CF; Schmidt, H; Kunkle, BW; Dunstan, ML; Ruiz, A; Bihoreau, MT; Reitz, C; Pasquier, F; Hollingworth, P; Hanon, O; Fitzpatrick, AL; Buxbaum, JD; Campion, D; Crane, PK; Becker, T; Gudnason, V; Cruchaga, C; Craig, D; Amin, N; Berr, C; Lopez, OL; De Jager, PL; Deramecourt, V; Johnston, JA; Evans, D; Lovestone, S; Letteneur, L; Kornhuber, J; Tarraga, L; Rubinsztein, DC; Eiriksdottir, G; Sleegers, K; Goate, AM; Fievet, N; Huentelman, MJ; Gill, M; Emilsson, V; Brown, K; Kamboh, MI; Keller, L; Barberger-Gateau, P; McGuinness, B; Larson, EB; Myers, AJ; Dufouil, C; Todd, S; Wallon, D; Love, S; Kehoe, P; Rogaeva, E; Gallacher, J; St George-Hyslop, P; Clarimon, J; Lleo, A; Bayer, A; Tsuang, DW; Yu, L; Tsolaki, M; Bossu, P; Spalletta, G; Proitsi, P; Collinge, J; Sorbi, S; Garcia, FS; Fox, N; Hardy, J; Naranjo, MCD; Razquin, C; Bosco, P; Clarke, R; Brayne, C; Galimberti, D; Mancuso, M; Moebus, S; Mecocci, P; del Zompo, M; Maier, W; Hampel, H; Pilotto, A; Bullido, M; Panza, F; Caffarra, P; Nacmias, B; Gilbert, JR; Mayhaus, M; Jessen, F; Dichgans, M; Lannfelt, L; Hakon, H; Pichler, S; Carrasquillo, MM; Ingelsson, M; Beekly, D; Alavarez, V; Zou, FG; Valladares, O; Younkin, SG; Coto, E; Hamilton-Nelson, KL; Mateo, I; Owen, MJ; Faber, KM; Jonsson, PV; Combarros, O; O'Donovan; MC Cantwell, LB; Soininen, H; Blacker, D; Mead, S; Mosley, TH; Bennett, DA; Harris, TB; Fratiglioni, L; Holmes, C; de Bruijn, RFAG; Passmore, P; Montine, TJ; Bettens, K; Rotter, JI; Brice, A; Morgan, K; Foroud, TM; Kukull, WA; Hannequin, D; Powell, JF; Nails, MA; Ritchie, K; Lunetta, KL; Kauwe, JSK; Boerwinkle, E; Riemenschneider, M; Boada, M; Hiltunen, M; Martin, ER; Pastor, P; Schmidt, R; Rujescu, D; Dartigues, JF; Mayeux, R; Tzourio, C; Hofman, A; Nothen, MM; Graff, C; Psaty, BM; Haines, JL; Lathrop, M; Pericak-Vance, MA; Launer, LJ; Farrer, LA; van Duijn, CM; Van Broeckhoven, C; Ramirez, A; Schellenberg, GD; Seshadri, S; Amouyel, P; Williams, J; Holmans, PA

Name:

Publisher version

Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item. When enough users have cast their vote on this item, the average rating will also be shown.

Star rating

Your vote was cast
Thank you for your feedback

Authors

Jones, L
Lambert, JC
Wang, LS
Choi, SH
Harold, D
Vedernikov, A
Escott-Price, V
Stone, T
Richards, A
Bellenguez,

Show all

Issue Date

2015-06

Metadata

Show full item record

Citation

Alzheimers Dement. 2015, 11 (6):658-71

Abstract

Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.
The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.
ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 × 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 × 10(-11)), cholesterol transport (P = 2.96 × 10(-9)), and proteasome-ubiquitin activity (P = 1.34 × 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).
The immune response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.

Description

To access publisher's full text version of this article click on the hyperlink at the bottom of the page

Additional Links

http://dx.doi.org/ 10.1016/j.jalz.2014.05.1757

Rights

Archived with thanks to Alzheimer's & dementia : the journal of the Alzheimer's Association

Collections

English Journal Articles (Peer Reviewed)