Title
Genome-wide association interaction analysis for Alzheimer's diseaseGenome-wide association interaction analysis for Alzheimer's disease
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
VIB DMG - Neurodegenerative Brain Diseases Group
Publication type
article
Publication
Fayetteville, N.Y.,
Subject
Human medicine
Source (journal)
Neurobiology of aging. - Fayetteville, N.Y.
Volume/pages
35(2014):11, p. 2436-2443
ISSN
0197-4580
ISI
000343419800004
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic datacombining strengths of different methods and statistical tools. The different steps of this protocol are illustrated on a real-life data application for Alzheimer's disease (AD) (2259 patients and 6017 controls from France). Particularly, in the exhaustive genome-wide epistasis screening we identified AD-associated interacting SNPs-pair from chromosome 6q11.1 (rs6455128, the KHDRBS2 gene) and 13q12.11 (rs7989332, the CRYL1 gene) (p = 0.006, corrected for multiple testing). A replication analysis in the independent AD cohort from Germany (555 patients and 824 controls) confirmed the discovered epistasis signal (p - 0.036). This signal was also supported by a meta-analysis approach in 5 independent AD cohorts that was applied in the context of epistasis for the first time. Transcriptome analysis revealed negative correlation between expression levels of KHDRBS2 and CRYL1 in both the temporal cortex (beta = -0.19, p = 0.0006) and cerebellum (beta = -0.23, p < 0.0001) brain regions. This is the first time a replicable epistasis associated with AD was identified using a hypothesis free screening approach. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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