Epistatic interaction of genetic depression risk variants in the human subgenual cingulate cortex during memory encoding.
Transl Psychiatry
; 4: e372, 2014 Mar 18.
Article
em En
| MEDLINE
| ID: mdl-24643163
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neuropeptídeos
/
Canais de Cálcio Tipo L
/
Proteínas do Citoesqueleto
/
Transtorno Depressivo Maior
/
Epistasia Genética
/
Memória Episódica
/
Giro do Cíngulo
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
Idioma:
En
Revista:
Transl Psychiatry
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha