Poster (Scientific congresses and symposiums)
Genome-wide Epistasis Screening for Alzheimer‘s Disease
Gusareva, Elena; Bellenguez, C; Sleegers, K et al.
2013The ACMG Annual Clinical Genetics Meeting
 

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Abstract :
[en] Objectives: Alzheimer disease (AlzD) is a complex, progressive neurodegenerative disease where dementia symptoms (memory and other intellectual abilities loss) gradually worsen over a number of years. The disease is characterized by the neuropathologic findings of neurofibrillary tangles and amyloid plaques that accumulate in vulnerable brain regions. AlzD is inherited as complex trait and appears to be highly heritable with 58-79 percent attributable to genetic factors. So far, although a number of main-effect genes have been identified, only a fraction of AlzD cases can be explained by specific gene mutations. In our study we performed an exhaustive and selective genome-wide screening for SNP-SNP interactions associated with AlzD in a large case/control cohort to reveal hidden heritability that can be accounted for by epistasis. Methods: We developed a minimal protocol for genome-wide association interaction (GWAI) analysis that involves screening over large-scale genomic data in the search for epistatic or synergetic effects. The protocol was applied on a large human cohort of 2,259 cases AlzD cases and 6,017 healthy controls from France to search for AlzD-associated epistasic effects. Results: In the exhaustive genome-wide screening, we identified two pairs of AlzD-associated interacting SNPs from chromosomes 6q11.1 and 13q12.11, and male-specific epistasis between SNPs from chromosomes 5q34 and 15q22.2. In the selective epistasis search, screening over the candidate genes for AlzD previously reported to be in interaction, we replicated seven out of twelve AlzD-associated gene pairs (INS / PPARA, IL1A / PPARA, IL10 / PPARA, TF / HFE, MTHFR / IL6, ABCA1 / NPC1, LRP1 / MAPT). Conclusion: It is the first time an epistasis study of this magnitude has been conducted in the context of AlzD. We show the advantages of viewing and analyzing data from different angles. A replication analysis strategy adapted to the epistasis detection context, as well as a meta-analytic approach confirmed effects of the discovered interactions. Apart from the biological and clinical importance, the present work offers a roadmap for future investigations in the field of epistasis detection and interpretation.
Disciplines :
Genetics & genetic processes
Author, co-author :
Gusareva, Elena ;  Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique
Bellenguez, C
Sleegers, K
Ertekin-Taner, N
Harold, D
Lambert, J-C
Van Steen, Kristel  ;  Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique
Language :
English
Title :
Genome-wide Epistasis Screening for Alzheimer‘s Disease
Publication date :
March 2013
Number of pages :
poster
Event name :
The ACMG Annual Clinical Genetics Meeting
Event place :
Phoenix, United States - Arizona
Event date :
19-23 - 03 - 2013
Audience :
International
Available on ORBi :
since 08 January 2015

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