학술논문

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease
Document Type
article
Author
Naj, Adam CJun, GyungahBeecham, Gary WWang, Li-SanVardarajan, Badri NarayanBuros, JacquelineGallins, Paul JBuxbaum, Joseph DJarvik, Gail PCrane, Paul KLarson, Eric BBird, Thomas DBoeve, Bradley FGraff-Radford, Neill RDe Jager, Philip LEvans, DenisSchneider, Julie ACarrasquillo, Minerva MErtekin-Taner, NiluferYounkin, Steven GCruchaga, CarlosKauwe, John SKNowotny, PetraKramer, PatriciaHardy, JohnHuentelman, Matthew JMyers, Amanda JBarmada, Michael MDemirci, F YesimBaldwin, Clinton TGreen, Robert CRogaeva, EkaterinaGeorge-Hyslop, Peter StArnold, Steven EBarber, RobertBeach, ThomasBigio, Eileen HBowen, James DBoxer, AdamBurke, James RCairns, Nigel JCarlson, Chris SCarney, Regina MCarroll, Steven LChui, Helena CClark, David GCorneveaux, JasonCotman, Carl WCummings, Jeffrey LDeCarli, CharlesDeKosky, Steven TDiaz-Arrastia, RamonDick, MalcolmDickson, Dennis WEllis, William GFaber, Kelley MFallon, Kenneth BFarlow, Martin RFerris, StevenFrosch, Matthew PGalasko, Douglas RGanguli, MaryGearing, MarlaGeschwind, Daniel HGhetti, BernardinoGilbert, John RGilman, SidGiordani, BrunoGlass, Jonathan DGrowdon, John HHamilton, Ronald LHarrell, Lindy EHead, ElizabethHonig, Lawrence SHulette, Christine MHyman, Bradley TJicha, Gregory AJin, Lee-WayJohnson, NancyKarlawish, JasonKarydas, AnnaKaye, Jeffrey AKim, RonaldKoo, Edward HKowall, Neil WLah, James JLevey, Allan ILieberman, Andrew PLopez, Oscar LMack, Wendy JMarson, Daniel CMartiniuk, FrankMash, Deborah CMasliah, EliezerMcCormick, Wayne CMcCurry, Susan MMcDavid, Andrew NMcKee, Ann CMesulam, MarselMiller, Bruce L
Source
Nature Genetics. 43(5)
Subject
Biological Sciences
Genetics
Acquired Cognitive Impairment
Dementia
Alzheimer's Disease
Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD)
Aging
Neurodegenerative
Neurosciences
Brain Disorders
Human Genome
2.1 Biological and endogenous factors
Aetiology
Neurological
Adaptor Proteins
Signal Transducing
Age of Onset
Aged
Aged
80 and over
Alzheimer Disease
Antigens
CD
Antigens
Differentiation
Myelomonocytic
Cohort Studies
Cytoskeletal Proteins
Databases
Genetic
Female
Genetic Predisposition to Disease
Genetic Variation
Genome-Wide Association Study
Humans
Male
Membrane Proteins
Multigene Family
Polymorphism
Single Nucleotide
Receptor
EphA1
Sialic Acid Binding Ig-like Lectin 3
Medical and Health Sciences
Developmental Biology
Agricultural biotechnology
Bioinformatics and computational biology
Language
Abstract
The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.