期刊
PLOS ONE
卷 9, 期 6, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0094661
关键词
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资金
- French National Foundation
- Institut Pasteur de Lille, Inserm, FRC (fondation pour la recherche sur le cerveau) and Rotary
- LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease)
- LABEX GENMED grant (Medical Genomics)
- IGAP
- National Foundation for Alzheimer's disease and related disorders, the Institut Pasteur de Lille and the Centre National de Genotypage
- The Fondation pour la Recherche Medicale
- Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, MGEN, Institut de la Longevite, Agence Francaise, de Securite Sanitaire des Produits de Sante
- ANR
- Eisai
- Belgian Science Policy Office Interuniversity Attraction Poles program
- Foundation Alzheimer Research (SAO-FRA)
- Flemish Government initiated Methusalem Excellence Program
- Research Foundation Flanders (FWO)
- University of Antwerp Research Fund, Belgium
- Health Research Council of the Academy of Finland
- Kuopio University Hospital [5772708]
- Nordic Centre of Excellence in Neurodegeneration
- Cassa di Risparmio di Pistoia e Pescia [2012]
- Cassa di Risparmio di Firenze [2012]
- Stichting MS Research
- Brain Net Europe
- Hersenstichting Nederland Breinbrekend Werk
- International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek
- Institut de Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona
- ADNI
- Abbott
- AstraZeneca AB
- Bayer Schering Pharma AG
- Bristol-Myers Squibb
- Eisai Global Clinical Development
- Elan Corporation
- Genentech
- GE Healthcare
- Glaxo-SmithKline
- Innogenetics
- Johnson and Johnson
- Eli Lilly and Co
- Medpace, Inc
- Merck and Co., Inc.
- Novartis AG
- Pfizer Inc
- F. Hoffman-La Roche
- Schering-Plough
- Synarc, Inc.
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Dana Foundation
- National Institute of Biomedical Imaging and Bioengineering
- NIA [U01 AG024904, RC2 AG036535, K01 AG030514]
- ADNI (National Institutes of Health) [U01 AG024904]
- National Institute on Aging
- The Canadian Institutes of Health Research
- NIH [K01 AG030514, P30 AG010129]
- Alzheimer Association (LAF) [IIRG-08-89720]
- Alzheimer Association (MP-V) [IIRG-05-14147]
- United States Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program
- Wellcome Trust
- Howard Hughes Medical Institute
- Canadian Institute of Health
- LABEX
- CNG
- EADI
- Aquitaine and Bourgogne Regional Councils, Agence Nationale de la Recherche
- [RF-2010-2319722]
- Alzheimers Research UK [ARUK-PG2014-2, ARUK-PG2014-1, ARUK-NCG2014A-1, ART-BIG2009-1] Funding Source: researchfish
- Alzheimer's Society [167, 164] Funding Source: researchfish
- Medical Research Council [MR/K013041/1, MR/L501517/1, MC_U123160651, MC_U137686857, G0902227, MR/L010305/1, MC_PC_14095, MC_U123192748] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10084, NF-SI-0512-10053, NF-SI-0513-10134, NF-SI-0508-10123] Funding Source: researchfish
- MRC [G0902227, MC_U123192748, MR/K013041/1, MC_U123160651, MC_U137686857, MC_PC_14095] Funding Source: UKRI
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 = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-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.
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