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Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Wednesday,2015-03-04 15:35 America/Los_Angeles — zdrager
| Title | Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease. |
| Publication Type | Journal Article |
| Year of Publication | 2014 |
| Authors | Escott-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, Ikram, AM, 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, Hernandez, 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/Institutional Authors | United Kingdom Brain Expression Consortium, Cardiovascular Health Study (CHS) |
| Journal | PLoS One |
| Volume | 9 |
| Issue | 6 |
| Pagination | e94661 |
| Date Published | 2014 |
| ISSN | 1932-6203 |
| Keywords | Alzheimer Disease, Carrier Proteins, Case-Control Studies, Genome-Wide Association Study, Heat-Shock Proteins, Humans, Polymorphism, Single Nucleotide, Receptors, Antigen, B-Cell |
| Abstract | <p><b>BACKGROUND: </b>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.</p><p><b>PRINCIPAL FINDINGS: </b>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.</p><p><b>SIGNIFICANCE: </b>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.</p> |
| DOI | 10.1371/journal.pone.0094661 |
| Alternate Journal | PLoS ONE |
| PubMed ID | 24922517 |
| PubMed Central ID | PMC4055488 |
| Grant List | 081864 / / Wellcome Trust / United Kingdom 089703 / / Wellcome Trust / United Kingdom 095317 / / Wellcome Trust / United Kingdom 100140 / / Wellcome Trust / United Kingdom 167 / / Alzheimer's Society / United Kingdom AG010491 / AG / NIA NIH HHS / United States AG019757 / AG / NIA NIH HHS / United States AG021547 / AG / NIA NIH HHS / United States AG023629 / AG / NIA NIH HHS / United States AG027058 / AG / NIA NIH HHS / United States AG027944 / AG / NIA NIH HHS / United States AG030653 / AG / NIA NIH HHS / United States AG033193 / AG / NIA NIH HHS / United States AG034504 / AG / NIA NIH HHS / United States AG041718 / AG / NIA NIH HHS / United States AG08122 / AG / NIA NIH HHS / United States AG15928 / AG / NIA NIH HHS / United States AG20098 / AG / NIA NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States HL080295 / HL / NHLBI NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States HL093029 / HL / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States K01 AG030514 / AG / NIA NIH HHS / United States K24HL038444 / HL / NHLBI NIH HHS / United States MC_U123192748 / / Medical Research Council / United Kingdom MC_U137686857 / / Medical Research Council / United Kingdom MH60451 / MH / NIMH NIH HHS / United States MR/K013041/1 / / Medical Research Council / United Kingdom MR/L010305/1 / / Medical Research Council / United Kingdom N01-AG-12100 / AG / NIA NIH HHS / United States NS39764 / NS / NINDS NIH HHS / United States P01 AG03991 / AG / NIA NIH HHS / United States P30 AG010124 / AG / NIA NIH HHS / United States P30 AG010129 / AG / NIA NIH HHS / United States P30 AG010161 / AG / NIA NIH HHS / United States P30 AG013846 / AG / NIA NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States P50 AG005133 / AG / NIA NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States P50 AG005136 / AG / NIA NIH HHS / United States P50 AG005142 / AG / NIA NIH HHS / United States P50 AG005142 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States P50 AG008671 / AG / NIA NIH HHS / United States P50 AG008671; / AG / NIA NIH HHS / United States P50 AG025688 / AG / NIA NIH HHS / United States P50AG005133 / AG / NIA NIH HHS / United States R01 AG017917 / AG / NIA NIH HHS / United States R01 AG019085 / AG / NIA NIH HHS / United States R01 AG034504 / AG / NIA NIH HHS / United States R01 AG037212 / AG / NIA NIH HHS / United States R01 AG041232 / AG / NIA NIH HHS / United States R01 AG041797 / AG / NIA NIH HHS / United States R01 HL096917 / HL / NHLBI NIH HHS / United States RC2 AG036535 / AG / NIA NIH HHS / United States RC2-HL102419 / HL / NHLBI NIH HHS / United States RF1 AG015819 / AG / NIA NIH HHS / United States U01 AG006781 / AG / NIA NIH HHS / United States U01 AG016976 / AG / NIA NIH HHS / United States U01 AG024904 / AG / NIA NIH HHS / United States U01 AG049505 / AG / NIA NIH HHS / United States U01 HG006375 / HG / NHGRI NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States UC2 HL103 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States UL1 TR001108 / TR / NCATS NIH HHS / United States |