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

Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Bellenguez, Céline, Wang, Li-San, Choi, Seung-Hoan, Harold, Denise ORCID: https://orcid.org/0000-0001-5195-0143, Jones, Lesley ORCID: https://orcid.org/0000-0002-3007-4612, Holmans, Peter ORCID: https://orcid.org/0000-0003-0870-9412, Gerrish, Amy, Vedernikov, Alexey, Richards, Alexander, DeStefano, Anita L., Lambert, Jean-Charles, Ibrahim-Verbaas, Carla A., Naj, Adam C., Sims, Rebecca ORCID: https://orcid.org/0000-0002-3885-1199, 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, Ikram, M. Arfan, Zelenika, Diana, Vardarajan, Badri N., Kamatani, Yoichiro, Lin, Chiao-Feng, Schmidt, Helena, Kunkle, Brian, Dunstan, Melanie L. ORCID: https://orcid.org/0000-0003-3817-2142, 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., Baldwin, Clinton, Becker, 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, George-Hyslop, Peter St, Clarimon, Jordi, Lleo, Alberto, Bayer, Anthony ORCID: https://orcid.org/0000-0002-7514-248X, Tsuang, Debby W., Yu, Lei, Tsolaki, Magda, Bossù, Paola, Spalletta, Gianfranco, Proitsi, Petra, Collinge, John, Sorbi, Sandro, Garcia, Florentino Sanchez, 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, Zompo, Maria Del, 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 ORCID: https://orcid.org/0000-0003-4798-0862, Faber, Kelley M., Jonsson, Palmi V., Combarros, Onofre, O'Donovan, Michael C. ORCID: https://orcid.org/0000-0001-7073-2379, Cantwell, Laura B., Soininen, Hilkka, Blacker, Deborah, Mead, Simon, Mosley Jr., 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 and Williams, Julie ORCID: https://orcid.org/0000-0002-4069-0259 2014. Gene-wide analysis detects two new susceptibility genes for Alzheimer's Disease. PLoS ONE 9 (6) , e94661. 10.1371/journal.pone.0094661

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Medicine Neuroscience and Mental Health Research Institute (NMHRI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Additional Information:	the United Kingdom Brain Expression Consortium
Publisher:	Public Library of Science
ISSN:	1932-6203
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	17 March 2014
Last Modified:	25 Oct 2024 01:20
URI:	https://orca.cardiff.ac.uk/id/eprint/74887

Citation Data

Cited 86 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item