The membrane-spanning 4-domains, subfamily A

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...

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Published in:Genome medicine 2011-05, Vol.3, p.33
Main Authors: Manzanares, Salvadora, Blanca, Irene, Antúnez, Carmen, Gayán, Javier, Vivancos-Moreau, Laura, Boada, Mercè, Lafuente, Asunción, Galán, José Jorge, Rosende-Roca, Maitée, López-Arrieta, Jesús, García, Blanca, Alegret, Montserrat, Vinyes, Georgina, Carrasco, José Miguel, Ruiz, Susana, Hernández, Isabel, Real, Luis Miguel, Becker, James T, Marín, Juan, Noguera-Perea, Fuensanta, González-Pérez, Antonio, Mauleón, Ana, Martínez-Herrada, Begoña, Tárraga, Lluís, Espinosa, Anna, Castaño, Sandra, Romo, Alejandro, Vázquez, Enrique, Sáez, María Eugenia, Moreno-Rey, Concha, López, Oscar L, Morón, Francisco Jesús, Ruiz, Agustín, Velasco, Juan, Legaz-García, Agustina, Ramírez-Lorca, Reposo, Serrano-Ríos, Manuel, Antequera-Torres, Martirio
Format: Article
Language:English
Subjects:
Alzheimer's disease
Genetic aspects
Genomes
Genomics
Medical research
Medicine, Experimental
Quality control
Online Access:Get full text
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Summary: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.
ISSN:1756-994X
1756-994X