Effect of rs1344706 in the ZNF804A gene on the brain network

Abstract

ZNF804A rs1344706 (A/C) was the first SNP that reached genome-wide significance for schizophrenia. Recent studies have linked rs1344706 to functional connectivity among specific brain regions. However, no study thus far has examined the role of this SNP in the entire functional connectome. In this study, we used degree centrality to test the role of rs1344706 in the whole-brain voxel-wise functional connectome during the resting state. 52 schizophrenia patients and 128 healthy controls were included in the final analysis. In our whole-brain analysis, we found a significant interaction effect of genotype×diagnosis at the precuneus (PCU) (cluster size=52 voxels, peak voxel MNI coordinates: x=9, y=−69, z=63, F=32.57, FWE corrected P<0.001). When we subdivided the degree centrality network according to anatomical distance, the whole-brain analysis also found a significant interaction effect of genotype×diagnosis at the PCU with the same peak in the short-range degree centrality network (cluster size=72 voxels, F=37.29, FWE corrected P<0.001). No significant result was found in the long-range degree centrality network. Our results elucidated the contribution of rs1344706 to functional connectivity within the brain network, and may have important implications for our understanding of this risk gene's role in functional dysconnectivity in schizophrenia. Keywords: ZNF804A, Schizophrenia, Functional magnetic resonance imaging, Degree centrality, Brain network, PCC/PCU