The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease

Background: In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population. Methods: We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 control...

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Detalles Bibliográficos
Autores: Antunez, Carmen, Boada, Mercè, González Pérez, Antonio, Gayán, Javier, Ramírez Lorca, Reposo, Marín, Juan, Sáez Ortega, María Loreto, Real Navarrete, Luis Miguel, Ruiz, Agustín
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:dnet:idus________::603f21f52bc31c0a9d6a502eb1b2060c
Acceso en línea:https://hdl.handle.net/11441/186179
https://doi.org/10.1186/gm249
Access Level:acceso abierto
Palabra clave:Genome Wide Association Study
Genome Wide Association Study Data
MS4A Family
Genome Wide Association Study Dataset
Bayesian Robust Linear Model
Descripción
Sumario:Background: In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population. Methods: We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study. To increase the power of the study, we combined our results with those of four other public GWAS datasets by applying identical quality control filters and the same imputation methods, which were then analyzed with a global meta-GWAS. A replication sample with 2,200 sporadic AD patients and 2,301 controls was genotyped to confirm our GWAS findings. Results: Meta-analysis of our data and independent replication datasets allowed us to confirm a novel genome-wide significant association of AD with the membrane-spanning 4-domains subfamily A (MS4A) gene cluster (rs1562990, P = 4.40E-11, odds ratio = 0.88, 95% confidence interval 0.85 to 0.91, n = 10,181 cases and 14,341 controls). Conclusions: Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases.