Research
The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease
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* Corresponding author: Agustín Ruiz aruiz@neocodex.es
- † Equal contributors
1 Dementia Unit, University Hospital Virgen de la Arrixaca, Ctra. Madrid-Cartagena, Murcia, s/n - 30120 El Palmar, Spain
2 Alzheimur Foundation, Avda. Juan Carlos, Building Cajamurcia, Murcia, 30100, Spain
3 Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Calle del Marqués de Sentmenat, Barcelona, 35-3708029, Spain
4 Hospital Universitari Vall d'Hebron - Institut de Recerca, Universitat Autònoma de Barcelona (VHIR-UAB), Carretera bellaterra, Barcelona, S/N 08290 Cerdanyola del Vallès, Spain
5 Department of Structural Genomics, Neocodex, Avda. Charles Darwin, Sevilla, s/n 41092, Spain
6 Memory Unit, University Hospital La Paz-Cantoblanco, Paseo Castellana, 261, Madrid, 28046, Spain
7 Alzheimer's Disease Research Center, Departments of Neurology, Psychiatry and Psychology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh PA, PA 15213-2536, USA
8 Diabetes Research Laboratory, Biomedical Research Foundation, University Hospital Clínico San Carlos, E - 28040, Madrid, Spain
Genome Medicine 2011, 3:33 doi:10.1186/gm249
Published: 31 May 2011Abstract
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.