TY - JOUR AU - Callicott, Joseph H. AU - Feighery, Emer L. AU - Mattay, Venkata S. AU - White, Michael G. AU - Chen, Qiang AU - Baranger, David A.A. AU - Berman, Karen F. AU - Lu, Bai AU - Song, Hongjun AU - Ming, Guo-li AU - Weinberger, Daniel R. T1 - DISC1 and SLC12A2 interaction affects human hippocampal function and connectivity PY - 2013/07/01/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI67510 VL - 123 IS - 7 UR - https://doi.org/10.1172/JCI67510 SP - 2961 EP - 2964 PB - The American Society for Clinical Investigation ER -