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

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, su...

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Autores principales:	Angela Heck, Christian Vogler, Leo Gschwind, Sandra Ackermann, Bianca Auschra, Klara Spalek, Björn Rasch, Dominique de Quervain, Andreas Papassotiropoulos
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d01bbfad25574b09a297a41d9e0aba13
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spelling	oai:doaj.org-article:d01bbfad25574b09a297a41d9e0aba132021-11-18T07:31:41ZStatistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory.1932-620310.1371/journal.pone.0029337https://doaj.org/article/d01bbfad25574b09a297a41d9e0aba132011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22216252/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Despite 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.Angela HeckChristian VoglerLeo GschwindSandra AckermannBianca AuschraKlara SpalekBjörn RaschDominique de QuervainAndreas PapassotiropoulosPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e29337 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angela Heck Christian Vogler Leo Gschwind Sandra Ackermann Bianca Auschra Klara Spalek Björn Rasch Dominique de Quervain Andreas Papassotiropoulos Statistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory.
description	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.
format	article
author	Angela Heck Christian Vogler Leo Gschwind Sandra Ackermann Bianca Auschra Klara Spalek Björn Rasch Dominique de Quervain Andreas Papassotiropoulos
author_facet	Angela Heck Christian Vogler Leo Gschwind Sandra Ackermann Bianca Auschra Klara Spalek Björn Rasch Dominique de Quervain Andreas Papassotiropoulos
author_sort	Angela Heck
title	Statistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory.
title_short	Statistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory.
title_full	Statistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory.
title_fullStr	Statistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory.
title_full_unstemmed	Statistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory.
title_sort	statistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/d01bbfad25574b09a297a41d9e0aba13
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Statistical epistasis and functional brain imaging support a role of voltage-gated potassium channels in human memory.

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