Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease
Copyright policy )Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease
We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).
- National Institutes of Health United States
- Amsterdam UMC Netherlands
- North Bristol NHS Trust United Kingdom
- Goethe University Frankfurt Germany
- University of Oxford United Kingdom
ABCA7 protein, human, Male, ATP-Binding Cassette Transporters/genetics, Signal Transducing/genetics, Sialic Acid Binding Ig-like Lectin 3, Medizin, genetics [Alzheimer Disease], Adaptor Proteins, Signal Transducing/genetics, Alzheimer's Disease, genetics [Adaptor Proteins, Signal Transducing], name=Cerebrovascular and Dementia Research Group, Databases, Genetic, 80 and over, Myelomonocytic/genetics, Aged, 80 and over, EMC NIHES-03-30-01, Alzheimer's disease, genetic predisposition, Receptor, EphA1, Antigens, CD/genetics, Adaptor Proteins, Single Nucleotide, genetics [Receptor, EphA1], ALZHEIMER’S DISEASE; GWAS; GENE-EXPRESSION; CLUSTERIN; APOE, genetics [Membrane Proteins], CD/genetics, genome-wide association; receptor tyrosine kinase; identifies variants; gene-expression; CLU; pilcalm; CR-1; risk; loci; apoe, Differentiation, EphA1/genetics, Multigene Family, alzheimer's disease, Genes & Society, Female, genetics [Antigens, Differentiation, Myelomonocytic], EMC COEUR-09, Receptor, /dk/atira/pure/subjectarea/asjc/1300/1311, EMC NIHES-01-64-01, EMC NIHES-01-64-02, name=Genetics, 610, Antigens, Differentiation, Myelomonocytic, Dementia@Manchester, Case-control studies, Cytoskeletal Proteins/genetics, ResearchInstitutes_Networks_Beacons/02/05; name=Dementia@Manchester, Polymorphism, Single Nucleotide, Article, Databases, CD33 protein, human, Genetic, Alzheimer Disease, Antigens, CD, Humans, Genetic Predisposition to Disease, /dk/atira/pure/subjectarea/asjc/1300/1311; name=Genetics, Antigens, Membrane Proteins/genetics, Polymorphism, genetics [Cytoskeletal Proteins], Adaptor Proteins, Signal Transducing, Aged, Alzheimer Disease/genetics, Antigens, Differentiation, Myelomonocytic/genetics, Genetic Variation, Membrane Proteins, CD2-associated protein, genetics [Antigens, CD], MS4A4E protein, human, Cytoskeletal Proteins, Case-Control Studies, ATP-Binding Cassette Transporters, genetics [ATP-Binding Cassette Transporters], aged, 80 and over, /dk/atira/pure/core/keywords/dementia_research_group, Receptor, EphA1/genetics, Genome-Wide Association Study, ddc: ddc:570
ABCA7 protein, human, Male, ATP-Binding Cassette Transporters/genetics, Signal Transducing/genetics, Sialic Acid Binding Ig-like Lectin 3, Medizin, genetics [Alzheimer Disease], Adaptor Proteins, Signal Transducing/genetics, Alzheimer's Disease, genetics [Adaptor Proteins, Signal Transducing], name=Cerebrovascular and Dementia Research Group, Databases, Genetic, 80 and over, Myelomonocytic/genetics, Aged, 80 and over, EMC NIHES-03-30-01, Alzheimer's disease, genetic predisposition, Receptor, EphA1, Antigens, CD/genetics, Adaptor Proteins, Single Nucleotide, genetics [Receptor, EphA1], ALZHEIMER’S DISEASE; GWAS; GENE-EXPRESSION; CLUSTERIN; APOE, genetics [Membrane Proteins], CD/genetics, genome-wide association; receptor tyrosine kinase; identifies variants; gene-expression; CLU; pilcalm; CR-1; risk; loci; apoe, Differentiation, EphA1/genetics, Multigene Family, alzheimer's disease, Genes & Society, Female, genetics [Antigens, Differentiation, Myelomonocytic], EMC COEUR-09, Receptor, /dk/atira/pure/subjectarea/asjc/1300/1311, EMC NIHES-01-64-01, EMC NIHES-01-64-02, name=Genetics, 610, Antigens, Differentiation, Myelomonocytic, Dementia@Manchester, Case-control studies, Cytoskeletal Proteins/genetics, ResearchInstitutes_Networks_Beacons/02/05; name=Dementia@Manchester, Polymorphism, Single Nucleotide, Article, Databases, CD33 protein, human, Genetic, Alzheimer Disease, Antigens, CD, Humans, Genetic Predisposition to Disease, /dk/atira/pure/subjectarea/asjc/1300/1311; name=Genetics, Antigens, Membrane Proteins/genetics, Polymorphism, genetics [Cytoskeletal Proteins], Adaptor Proteins, Signal Transducing, Aged, Alzheimer Disease/genetics, Antigens, Differentiation, Myelomonocytic/genetics, Genetic Variation, Membrane Proteins, CD2-associated protein, genetics [Antigens, CD], MS4A4E protein, human, Cytoskeletal Proteins, Case-Control Studies, ATP-Binding Cassette Transporters, genetics [ATP-Binding Cassette Transporters], aged, 80 and over, /dk/atira/pure/core/keywords/dementia_research_group, Receptor, EphA1/genetics, Genome-Wide Association Study, ddc: ddc:570
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