DISC1 and SLC12A2 interaction affects human hippocampal function and connectivity

Joseph H. Callicott, Emer L. Feighery, Venkata S. Mattay, Michael G. White, Qiang Chen, David A.A. Baranger, Karen F. Berman, Bai Lu, Hongjun Song, Guo Li Ming, Daniel R. Weinberger

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2961-2964
Number of pages4
JournalJournal of Clinical Investigation
Volume123
Issue number7
DOIs
StatePublished - Jul 1 2013

ASJC Scopus subject areas

  • Medicine(all)

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    Callicott, J. H., Feighery, E. L., Mattay, V. S., White, M. G., Chen, Q., Baranger, D. A. A., Berman, K. F., Lu, B., Song, H., Ming, G. L., & Weinberger, D. R. (2013). DISC1 and SLC12A2 interaction affects human hippocampal function and connectivity. Journal of Clinical Investigation, 123(7), 2961-2964. https://doi.org/10.1172/JCI67510