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


ABSTRACT: In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population.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.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).Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases.

SUBMITTER: Antunez C 

PROVIDER: S-EPMC3219074 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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

Antúnez Carmen C   Boada Mercè M   González-Pérez Antonio A   Gayán Javier J   Ramírez-Lorca Reposo R   Marín Juan J   Hernández Isabel I   Moreno-Rey Concha C   Morón Francisco Jesús FJ   López-Arrieta Jesús J   Mauleón Ana A   Rosende-Roca Maitée M   Noguera-Perea Fuensanta F   Legaz-García Agustina A   Vivancos-Moreau Laura L   Velasco Juan J   Carrasco José Miguel JM   Alegret Montserrat M   Antequera-Torres Martirio M   Manzanares Salvadora S   Romo Alejandro A   Blanca Irene I   Ruiz Susana S   Espinosa Anna A   Castaño Sandra S   García Blanca B   Martínez-Herrada Begoña B   Vinyes Georgina G   Lafuente Asunción A   Becker James T JT   Galán José Jorge JJ   Serrano-Ríos Manuel M   Vázquez Enrique E   Tárraga Lluís L   Sáez María Eugenia ME   López Oscar L OL   Real Luis Miguel LM   Ruiz Agustín A  

Genome medicine 20110531 5


<h4>Background</h4>In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population.<h4>Methods</h4>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 pub  ...[more]

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