1. DISC1 and SLC12A2 interaction affects human hippocampal function and connectivity
- Author
-
Karen F. Berman, Michael G. White, Joseph H. Callicott, David A.A. Baranger, Guo Li Ming, Qiang Chen, Bai Lu, Emer L. Feighery, Hongjun Song, Daniel R. Weinberger, and Venkata S. Mattay
- Subjects
Adult ,Heterozygote ,Adolescent ,Sodium-Potassium-Chloride Symporters ,Hippocampus ,Nerve Tissue Proteins ,Hippocampal formation ,Neurotransmission ,Polymorphism, Single Nucleotide ,Young Adult ,DISC1 ,Connectome ,medicine ,Humans ,Solute Carrier Family 12, Member 2 ,Genetic Predisposition to Disease ,Recognition memory ,Genetics ,biology ,Brief Report ,Epistasis, Genetic ,Depolarization ,General Medicine ,Middle Aged ,Phenotype ,medicine.anatomical_structure ,Schizophrenia ,biology.protein ,Parahippocampal Gyrus ,Neuroscience ,Parahippocampal gyrus - Abstract
Hippocampal development is coordinated by both extracellular factors like GABA neurotransmission and intracellular components like DISC1. We previously reported that SLC12A2-dependent GABA depolarization and DISC1 coregulate hippocampal neuronal development, and 2 SNPs in these genes linked to mRNA expression interactively increase schizophrenia risk. Using functional MRI, we now confirm this biological interaction in vivo by showing in 2 independent samples of healthy individuals (total N = 349) that subjects homozygous for both risk alleles evince dramatically decreased hippocampal area activation (Cohen’s d = 0.78) and connectivity (d = 0.57) during a recognition memory task. These data highlight the importance of epistatic models in understanding genetic association with complex brain phenotypes.
- Published
- 2013
- Full Text
- View/download PDF