Publication
Title
Male-specific epistasis between WWC1 and TLN2 genes is associated with Alzheimer's disease
Author
Institution/Organisation
Genetic Environmental Risk
Alzheimers Dis Genetics Consortium
European Alzheimer Dis Initiative
Abstract
Systematic epistasis analyses in multifactorial disorders are an important step to better characterize complex genetic risk structures. We conducted a hypothesis-free sex-stratified genome-wide screening for epistasis contributing to Alzheimer's disease (AD) susceptibility. We identified a statistical epistasis signal between the single nucleotide polymorphisms rs3733980 and rs7175766 that was associated with AD in males (genome-wide significant p(Bonferroni-corrected) = 0.0165). This signal pointed toward the genes WW and C2 domain containing 1, aka KIBRA; 5q34 and TLN2 (talin 2; 15q22.2). Gene-based meta-analysis in 3 independent consortium data sets confirmed the identified interaction: the most significant (metaBonferroni- corrected = 9.02*10(-3)) was for the single nucleotide polymorphism pair rs1477307 and rs4077746. In functional studies, WWand C2 domain containing 1, aka KIBRA and TLN2 coexpressed in the temporal cortex brain tissue of AD subjects (beta = 0.17, 95% CI 0.04 to 0.30, p = 0.01); modulated Tau toxicity in Drosophila eye experiments; colocalized in brain tissue cells, N2a neuroblastoma, and HeLa cell lines; and coimmunoprecipitated both in brain tissue and HEK293 cells. Our finding points toward new AD-related pathways and provides clues toward novel medical targets for the cure of AD. (C) 2018 Elsevier Inc. All rights reserved.
Language
English
Source (journal)
Neurobiology of aging. - Fayetteville, N.Y.
Publication
Fayetteville, N.Y. : 2018
ISSN
0197-4580
Volume/pages
72 (2018) , 10 p.
Article Reference
188.e3
ISI
000449073700025
Pubmed ID
30201328
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 10.12.2018
Last edited 20.09.2021
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