This title appears in the Scientific Report :
2014
Please use the identifier:
http://hdl.handle.net/2128/5973 in citations.
Please use the identifier: http://dx.doi.org/10.1038/tp.2014.10 in citations.
Epistatic interaction of genetic depression risk variants in the human subgenual cingulate cortex during memory encoding
Epistatic interaction of genetic depression risk variants in the human subgenual cingulate cortex during memory encoding
Recent genome-wide association studies have pointed to single-nucleotide polymorphisms (SNPs) in genes encoding the neuronal calcium channel CaV1.2 (CACNA1C; rs1006737) and the presynaptic active zone protein Piccolo (PCLO; rs2522833) as risk factors for affective disorders, particularly major depre...
Saved in:
Personal Name(s): | Schott, B. H. (Corresponding Author) |
---|---|
Assmann, A. / Schmierer, P. / Soch, J. / Erk, S. / Garbusow, M. / Mohnke, S. / Pöhland, L. / Romanczuk-Seiferth, N. / Barman, A. / Wüstenberg, T. / Haddad, L. / Grimm, O. / Witt, S. / Richter, S. / Klein, M. / Schütze, H. / Mühleisen, Thomas / Cichon, S. / Rietschel, M. / Noethen, M. M. / Tost, H. / Gundelfinger, E. D. / Düzel, E. / Heinz, A. / Meyer-Lindenberg, A. / Seidenbecher, C. I. / Walter, H. | |
Contributing Institute: |
Strukturelle und funktionelle Organisation des Gehirns; INM-1 |
Published in: | Translational Psychiatry, 4 (2014) 3, S. e372 |
Imprint: |
London
Nature Publishing Group
2014
|
PubMed ID: |
24643163 |
DOI: |
10.1038/tp.2014.10 |
Document Type: |
Journal Article |
Research Program: |
Connectivity and Activity Pathophysiological Mechanisms of Neurological and Psychiatric Diseases |
Link: |
OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1038/tp.2014.10 in citations.
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520 | |a Recent genome-wide association studies have pointed to single-nucleotide polymorphisms (SNPs) in genes encoding the neuronal calcium channel CaV1.2 (CACNA1C; rs1006737) and the presynaptic active zone protein Piccolo (PCLO; rs2522833) as risk factors for affective disorders, particularly major depression. Previous neuroimaging studies of depression-related endophenotypes have highlighted the role of the subgenual cingulate cortex (CG25) in negative mood and depressive psychopathology. Here, we aimed to assess how recently associated PCLO and CACNA1C depression risk alleles jointly affect memory-related CG25 activity as an intermediate phenotype in clinically healthy humans. To investigate the combined effects of rs1006737 and rs2522833 on the CG25 response, we conducted three functional magnetic resonance imaging studies of episodic memory formation in three independent cohorts (N=79, 300, 113). An epistatic interaction of PCLO and CACNA1C risk alleles in CG25 during memory encoding was observed in all groups, with carriers of no risk allele and of both risk alleles showing higher CG25 activation during encoding when compared with carriers of only one risk allele. Moreover, PCLO risk allele carriers showed lower memory performance and reduced encoding-related hippocampal activation. In summary, our results point to region-specific epistatic effects of PCLO and CACNA1C risk variants in CG25, potentially related to episodic memory. Our data further suggest that genetic risk factors on the SNP level do not necessarily have additive effects but may show complex interactions. Such epistatic interactions might contribute to the ‘missing heritability’ of complex phenotypes. | ||
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