Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
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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.
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The record
- Venue
- PLoS ONE
- Topic
- Alzheimer's disease research and treatments
- Field
- Medicine
- Canadian institutions
- Occupational Cancer Research CentreMcGill University and Génome Québec Innovation CentreUniversity of Toronto
- Funders
- National Center for Advancing Translational SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesNational Center for Research ResourcesNational Institute of General Medical SciencesNational Cancer InstituteNational Human Genome Research InstituteNational Institute of Mental HealthNational Institute on AgingInstituto de Salud Carlos IIIMenzies Centre for Australian Studies, King's College London, University of LondonUniversity of California, San FranciscoUniversity of California, DavisNational Institutes of HealthHeinz Nixdorf StiftungHjartaverndH. Lundbeck A/SKarl-Franzens-Universität GrazUniversity of PennsylvaniaAustrian Science FundMedizinische Universität GrazInternationale Stichting Alzheimer OnderzoekNational Institute of Child Health and Human DevelopmentHersenstichtingMedical Research CouncilSwedish Brain PowerNational Institute of Neurological Disorders and StrokeLlywodraeth CymruDeutsches Zentrum für Neurodegenerative ErkrankungenNational Heart, Lung, and Blood InstituteNorth Bristol NHS TrustVetenskapsrådetUniversity of PittsburghStockholms Läns LandstingMarcus och Amalia Wallenbergs minnesfondErasmus Medisch CentrumBundesministerium für Bildung und ForschungKarolinska InstitutetZonMwAgence Nationale de la RechercheSchool of Medicine, Boston UniversityEuropean CommissionCentro de Biología Molecular Severo OchoaCardiff UniversityAlzheimer's Research TrustUniversity of California, IrvineUniversity College London Hospitals NHS Foundation TrustUniversity of California, Los AngelesUniversity of WashingtonUniversity of California, San DiegoJohns Hopkins UniversityNational Institute on Deafness and Other Communication DisordersRush UniversityUniversity of MiamiYork UniversityNorthwestern UniversityMinistero della SaluteAlzheimer's SocietyNational Eye InstituteNational Institute for Health and Care ResearchAlzheimer SocietyNewcastle UniversityVanderbilt UniversityWellcome TrustUniversity of Southern CaliforniaMassachusetts General HospitalEmory UniversityJuvenile Diabetes Research Foundation International
- Keywords
- GeneticsBiologyGeneGenome-wide association studyDiseaseAlzheimer's diseaseDementiaGenomeGenetic associationGenotypeSingle-nucleotide polymorphismMedicinePathology
- Has abstract in OpenAlex
- yes