Journal article

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

Eduardo Perez-Palma, Bernabe I Bustos, Camilo F Villaman, Marcelo A Alarcon, Miguel E Avila, Giorgia D Ugarte, Ariel E Reyes, Carlos Opazo, Giancarlo V De Ferrari

PLoS One | PUBLIC LIBRARY SCIENCE | Published : 2014

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 ..

View full abstract

Grants

Awarded by Chilean Government FONDECYT


Awarded by FONDAP


Awarded by MECESUP


Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES


Awarded by NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

This work was supported by Grants from the Chilean Government FONDECYT 1100942 and FONDAP 15090007 to GVD. EP-P and MEA are supported by doctoral fellowships from CONICYT. BIB is supported by a doctoral fellowship by MECESUP UAB0802. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.