Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 123, Issue 7, Pages 2961-2964Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI67510
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- NIMH
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Hippocampal development is coordinated by both extracellular factors like GABA neurotransmission and intracellular components like DISCI. 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.
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