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

TitleGene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2014
AuthorsEscott-Price, V, Bellenguez, C, San Wang, L-, Choi, S-H, Harold, D, Jones, L, Holmans, P, Gerrish, A, Vedernikov, A, Richards, A, DeStefano, AL, Lambert, J-C, Ibrahim-Verbaas, CA, Naj, AC, Sims, R, Jun, G, Bis, JC, Beecham, GW, Grenier-Boley, B, Russo, G, Thornton-Wells, TA, Denning, N, Smith, AV, Chouraki, V, Thomas, C, M Ikram, A, Zelenika, D, Vardarajan, BN, Kamatani, Y, Lin, C-F, Schmidt, H, Kunkle, B, Dunstan, ML, Vronskaya, M, Johnson, AD, Ruiz, A, Bihoreau, M-T, Reitz, C, Pasquier, F, Hollingworth, P, Hanon, O, Fitzpatrick, AL, Buxbaum, JD, Campion, D, Crane, PK, Baldwin, C, 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, Letenneur, L, Hernández, I, Rubinsztein, DC, Eiriksdottir, G, Sleegers, K, Goate, AM, Fiévet, N, Huentelman, MJ, Gill, M, Brown, K, M Kamboh, I, Keller, L, Barberger-Gateau, P, McGuinness, B, Larson, EB, Myers, AJ, Dufouil, C, Todd, S, Wallon, D, Love, S, Rogaeva, E, Gallacher, J, St George-Hyslop, P, Clarimon, J, Lleo, A, Bayer, A, Tsuang, DW, Yu, L, Tsolaki, M, Bossù, P, Spalletta, G, Proitsi, P, Collinge, J, Sorbi, S, Garcia, FSanchez, Fox, NC, Hardy, J, Naranjo, MCandida De, Bosco, P, Clarke, R, Brayne, C, Galimberti, D, Scarpini, E, Bonuccelli, U, Mancuso, M, Siciliano, G, Moebus, S, Mecocci, P, Del Zompo, M, Maier, W, Hampel, H, Pilotto, A, Frank-García, A, Panza, F, Solfrizzi, V, Caffarra, P, Nacmias, B, Perry, W, Mayhaus, M, Lannfelt, L, Hakonarson, H, Pichler, S, Carrasquillo, MM, Ingelsson, M, Beekly, D, Alvarez, V, Zou, F, Valladares, O, Younkin, SG, Coto, E, Hamilton-Nelson, KL, Gu, W, Razquin, C, Pastor, P, 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, Nalls, MA, Ritchie, K, Lunetta, KL, Kauwe, JSK, Boerwinkle, E, Riemenschneider, M, Boada, M, Hiltunen, M, Martin, ER, Schmidt, R, Rujescu, D, Dartigues, J-F, Mayeux, R, Tzourio, C, Hofman, A, Nöthen, MM, Graff, C, Psaty, BM, Haines, JL, Lathrop, M, Pericak-Vance, MA, Launer, LJ, Van Broeckhoven, C, Farrer, LA, van Duijn, CM, Ramirez, A, Seshadri, S, Schellenberg, GD, Amouyel, P, Williams, J
Corporate AuthorsUnited Kingdom Brain Expression Consortium, Cardiovascular Health Study (CHS)
JournalPLoS One
Volume9
Issue6
Paginatione94661
Date Published2014
ISSN1932-6203
KeywordsAlzheimer Disease, Carrier Proteins, Case-Control Studies, Genome-Wide Association Study, Heat-Shock Proteins, Humans, Polymorphism, Single Nucleotide, Receptors, Antigen, B-Cell
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.

DOI10.1371/journal.pone.0094661
Alternate JournalPLoS One
PubMed ID24922517
PubMed Central IDPMC4055488
Grant ListUC2 HL103 / HL / NHLBI NIH HHS / United States
P50 AG008671; / AG / NIA NIH HHS / United States
P30 AG013854 / AG / NIA NIH HHS / United States
N01HC55020 / HL / NHLBI NIH HHS / United States
167 / ALZS_ / Alzheimer's Society / United Kingdom
P50 MH060451 / MH / NIMH NIH HHS / United States
K01 AG030514 / AG / NIA NIH HHS / United States
MH60451 / MH / NIMH NIH HHS / United States
P50AG005133 / AG / NIA NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
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RC2-HL102419 / HL / NHLBI NIH HHS / United States
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UC2 HL103010 / HL / NHLBI NIH HHS / United States
AG027058 / AG / NIA NIH HHS / United States
M01 RR000096 / RR / NCRR NIH HHS / United States
RC2 AG036528 / AG / NIA NIH HHS / United States
AG15928 / AG / NIA NIH HHS / United States
P30 AG028377 / AG / NIA NIH HHS / United States
MC_U137686857 / MRC_ / Medical Research Council / United Kingdom
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N01AG12100 / AG / NIA NIH HHS / United States
T32 GM008151 / GM / NIGMS NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
G0902227 / MRC_ / Medical Research Council / United Kingdom
P50 AG008671 / AG / NIA NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
P50 AG005142 / AG / NIA NIH HHS / United States
R01 AG016495 / AG / NIA NIH HHS / United States
MC_U123160651 / MRC_ / Medical Research Council / United Kingdom
MC_U123192748 / MRC_ / Medical Research Council / United Kingdom
UL1 RR025005 / RR / NCRR NIH HHS / United States
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HL105756 / HL / NHLBI NIH HHS / United States
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HHSN268200800007C / HL / NHLBI NIH HHS / United States
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MR/L010305/1 / MRC_ / Medical Research Council / United Kingdom
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