Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Ontology highlight
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.
SUBMITTER: Escott-Price V
PROVIDER: S-EPMC4055488 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Escott-Price Valentina V Bellenguez Céline C Wang Li-San LS Choi Seung-Hoan SH Harold Denise D Jones Lesley L Holmans Peter P Gerrish Amy A Vedernikov Alexey A Richards Alexander A DeStefano Anita L AL Lambert Jean-Charles JC Ibrahim-Verbaas Carla A CA Naj Adam C AC Sims Rebecca R Jun Gyungah G Bis Joshua C JC Beecham Gary W GW Grenier-Boley Benjamin B Russo Giancarlo G Thornton-Wells Tricia A TA Denning Nicola N Smith Albert V AV Chouraki Vincent V Thomas Charlene C Ikram M Arfan MA Zelenika Diana D Vardarajan Badri N BN Kamatani Yoichiro Y Lin Chiao-Feng CF Schmidt Helena H Kunkle Brian B Dunstan Melanie L ML Vronskaya Maria M Johnson Andrew D AD Ruiz Agustin A Bihoreau Marie-Thérèse MT Reitz Christiane C Pasquier Florence F Hollingworth Paul P Hanon Olivier O Fitzpatrick Annette L AL Buxbaum Joseph D JD Campion Dominique D Crane Paul K PK Baldwin Clinton C Becker Tim T Gudnason Vilmundur V Cruchaga Carlos C Craig David D Amin Najaf N Berr Claudine C Lopez Oscar L OL De Jager Philip L PL Deramecourt Vincent V Johnston Janet A JA Evans Denis D Lovestone Simon S Letenneur Luc L Hernández Isabel I Rubinsztein David C DC Eiriksdottir Gudny G Sleegers Kristel K Goate Alison M AM Fiévet Nathalie N Huentelman Matthew J MJ Gill Michael M Brown Kristelle K Kamboh M Ilyas MI Keller Lina L Barberger-Gateau Pascale P McGuinness Bernadette B Larson Eric B EB Myers Amanda J AJ Dufouil Carole C Todd Stephen S Wallon David D Love Seth S Rogaeva Ekaterina E Gallacher John J George-Hyslop Peter St PS Clarimon Jordi J Lleo Alberto A Bayer Anthony A Tsuang Debby W DW Yu Lei L Tsolaki Magda M Bossù Paola P Spalletta Gianfranco G Proitsi Petra P Collinge John J Sorbi Sandro S Garcia Florentino Sanchez FS Fox Nick C NC Hardy John J Naranjo Maria Candida Deniz MC Bosco Paolo P Clarke Robert R Brayne Carol C Galimberti Daniela D Scarpini Elio E Bonuccelli Ubaldo U Mancuso Michelangelo M Siciliano Gabriele G Moebus Susanne S Mecocci Patrizia P Zompo Maria Del MD Maier Wolfgang W Hampel Harald H Pilotto Alberto A Frank-García Ana A Panza Francesco F Solfrizzi Vincenzo V Caffarra Paolo P Nacmias Benedetta B Perry William W Mayhaus Manuel M Lannfelt Lars L Hakonarson Hakon H Pichler Sabrina S Carrasquillo Minerva M MM Ingelsson Martin M Beekly Duane D Alvarez Victoria V Zou Fanggeng F Valladares Otto O Younkin Steven G SG Coto Eliecer E Hamilton-Nelson Kara L KL Gu Wei W Razquin Cristina C Pastor Pau P Mateo Ignacio I Owen Michael J MJ Faber Kelley M KM Jonsson Palmi V PV Combarros Onofre O O'Donovan Michael C MC Cantwell Laura B LB Soininen Hilkka H Blacker Deborah D Mead Simon S Mosley Thomas H TH Bennett David A DA Harris Tamara B TB Fratiglioni Laura L Holmes Clive C de Bruijn Renee F A G RF Passmore Peter P Montine Thomas J TJ Bettens Karolien K Rotter Jerome I JI Brice Alexis A Morgan Kevin K Foroud Tatiana M TM Kukull Walter A WA Hannequin Didier D Powell John F JF Nalls Michael A MA Ritchie Karen K Lunetta Kathryn L KL Kauwe John S K JS Boerwinkle Eric E Riemenschneider Matthias M Boada Mercè M Hiltunen Mikko M Martin Eden R ER Schmidt Reinhold R Rujescu Dan D Dartigues Jean-François JF Mayeux Richard R Tzourio Christophe C Hofman Albert A Nöthen Markus M MM Graff Caroline C Psaty Bruce M BM Haines Jonathan L JL Lathrop Mark M Pericak-Vance Margaret A MA Launer Lenore J LJ Van Broeckhoven Christine C Farrer Lindsay A LA van Duijn Cornelia M CM Ramirez Alfredo A Seshadri Sudha S Schellenberg Gerard D GD Amouyel Philippe P Williams Julie J
PloS one 20140612 6
<h4>Background</h4>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 genotype ...[more]