Overrepresentation of Glutamate Signaling in Alzheimer's Disease: Network-Based Pathway Enrichment Using Meta-Analysis of Genome-Wide Association Studies

Eduardo Pérez-Palma, Bernabé I Bustos, Camilo F Villamán, Marcelo A Alarcón, Miguel E Avila, Giorgia D Ugarte, Ariel E Reyes, Carlos Opazo, Giancarlo V De Ferrari, the Alzheimer's Disease Neuroimaging Initiative and the NIA-LOAD/NCRAD Family Study Group

PLOS ONE, 2014, vol. 9, issue 4, 1-16

Abstract: Genome-wide association studies (GWAS) have successfully identified several risk loci for Alzheimer's disease (AD). Nonetheless, these loci do not explain the entire susceptibility of the disease, suggesting that other genetic contributions remain to be identified. Here, we performed a meta-analysis combining data of 4,569 individuals (2,540 cases and 2,029 healthy controls) derived from three publicly available GWAS in AD and replicated a broad genomic region (>248,000 bp) associated with the disease near the APOE/TOMM40 locus in chromosome 19. To detect minor effect size contributions that could help to explain the remaining genetic risk, we conducted network-based pathway analyses either by extracting gene-wise p-values (GW), defined as the single strongest association signal within a gene, or calculated a more stringent gene-based association p-value using the extended Simes (GATES) procedure. Comparison of these strategies revealed that ontological sub-networks (SNs) involved in glutamate signaling were significantly overrepresented in AD (p

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0095413

DOI: 10.1371/journal.pone.0095413

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