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Genome Med. 2011 May 31;3(5):33. doi: 10.1186/gm249.

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

Author information

  • 1Department of Structural Genomics, Neocodex, Avda, Charles Darwin, Sevilla, s/n 41092, Spain. aruiz@neocodex.es.

Abstract

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.

PMID:
21627779
[PubMed]
PMCID:
PMC3219074
Free PMC Article

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