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Statistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2011
Author Heck Angela, Vogler Christian, Gschwind Leo, Ackermann Sandra, Auschra Bianca, Spalek Klara, Rasch Björn, de Quervain Dominique, Papassotiropoulos Andreas,
Project KRAB/KAP1 epigenetic regulation in the control of memory and emotional traits: from mice to humans.
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Original article (peer-reviewed)

Journal PloS one
Volume (Issue) 6(12)
Page(s) 29337 - 29337
Title of proceedings PloS one
DOI 10.1371/journal.pone.0029337


Despite the current progress in high-throughput, dense genome scans, a major portion of complex traits' heritability still remains unexplained, a phenomenon commonly termed "missing heritability." The negligence of analytical approaches accounting for gene-gene interaction effects, such as statistical epistasis, is probably central to this phenomenon. Here we performed a comprehensive two-way SNP interaction analysis of human episodic memory, which is a heritable complex trait, and focused on 120 genes known to show differential, memory-related expression patterns in rat hippocampus. Functional magnetic resonance imaging was also used to capture genotype-dependent differences in memory-related brain activity. A significant, episodic memory-related interaction between two markers located in potassium channel genes (KCNB2 and KCNH5) was observed (P(nominal combined) = 0.000001). The epistatic interaction was robust, as it was significant in a screening (P(nominal) = 0.0000012) and in a replication sample (P(nominal) = 0.01). Finally, we found genotype-dependent activity differences in the parahippocampal gyrus (P(nominal) = 0.001) supporting the behavioral genetics finding. Our results demonstrate the importance of analytical approaches that go beyond single marker statistics of complex traits.