DISC1 and SLC12A2 interaction affects human hippocampal function and connectivity
JH Callicott, EL Feighery, VS Mattay… - The Journal of …, 2013 - Am Soc Clin Investig
The Journal of clinical investigation, 2013•Am Soc Clin Investig
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 …
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 …
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.
The Journal of Clinical Investigation