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- Title
DISC1 and SLC12A2 interaction affects human hippocampal function and connectivity.
- Authors
Callicott, Joseph H; Feighery, Emer L; Mattay, Venkata S; White, Michael G; Chen, Qiang; Baranger, David A A; Berman, Karen F; Lu, Bai; Song, Hongjun; Ming, Guo-li; Weinberger, Daniel R
- 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.
- Publication
The Journal of clinical investigation, 2013, Vol 123, Issue 7, p2961
- ISSN
1558-8238
- Publication type
Journal Article
- DOI
10.1172/JCI67510