ZNF804A rs1344706 is associated with cortical thickness, surface area, and cortical volume of the unmedicated first episode schizophrenia and healthy controls

Abstract

The effects of ZNF804A rs1344706, a prominent susceptibility gene for schizophrenia, on gray matter (GM) structure in unmedicated schizophrenia (SZ) patients are still unknown, although several previous studies investigated the effects in medicated SZ patients and healthy controls (HC). Analyzing cortical thickness, surface area, and GM volume simultaneously may provide a more precise and complete picture of the effects. We genotyped 59 unmedicated first episode SZ patients and 60 healthy controls for the ZNF804A single nucleotide polymorphism (SNP) rs1344706, and examined between-group differences in cortical thickness, surface area, and cortical volume using a full-factorial 2 × 2 analysis of variance (ANOVA). We found the risk allele (T) in ZNF804A rs1344706, compared to the non-risk allele (G), was associated with thinner cortex in the bilateral precuneus, left precentral gyrus, and several other regions, associated with a smaller cortical surface area in the left superior parietal, precuneus cortex and left superior frontal, and associated with a lower cortical volume in the left superior frontal, left precentral, and right precuneus in SZ patients. In contrast, in the controls, the T allele was associated with the increased cortical measurements compared to the G allele in the same regions as those mentioned above. ZNF804A rs1344706 has significant, but different, effects on cortical thickness, surface area, and cortical volume in multiple regions of the brain cortex. Our findings suggest that ZNF804A rs1344706 may aggravate the risk for schizophrenia by exerting its effects on cortical thickness, surface area, and cortical volume in these brain regions.

Predicting brain structure in population‐based samples with biologically informed genetic scores for schizophrenia

“…Investigations of single schizophrenia‐associated variants on brain structure in healthy individuals did not report consistent results. For many candidate SNPs no link between the genetics of schizophrenia and brain volumes could be found [Liu et al, ; Cousijn et al, ], although some studies did report significant associations [Erk et al, ; Wei et al, ]. Nevertheless, there are some methodological key questions for single SNP association studies, (i) is the assumption of a single causal SNP effect valid, if a polygenic nature of the phenotype of interest is assumed?…”

Postnatal neurodevelopmental expression and glutamate-dependent regulation of the ZNF804A rodent homologue

“…It was the first gene to reach genome-wide significance for psychosis (O'Donovan et al, 2008) and its association with both schizophrenia and bipolar disorder has been subsequently confirmed in multiple genome-wide association studies (GWASs; Riley et al, 2010; Williams et al, 2011; Zhang et al, 2011). Studies of the single nucleotide polymorphism (SNP) rs1344706 in both psychiatric patients and healthy risk allele carriers have demonstrated effects on white and gray matter volume, white matter tract integrity, functional connectivity (Esslinger et al, 2009; Ikuta et al, 2014; Lencz et al, 2010; Voineskos et al, 2011; Wei et al, 2015), and cognition (Chen et al, 2012; Esslinger et al, 2011; Hashimoto et al, 2010; Walter et al, 2011; Walters et al, 2010), indicating potential functional consequences of this gene variant.…”

Genetic association of rs1344706 in ZNF804A with bipolar disorder and schizophrenia susceptibility in Chinese populations

“…Three samples394041 were, therefore, excluded from the final meta-analysis as a result of partial overlap with other larger samples1317. Besides, several genome-wide association studies (GWAS) of schizophrenia conducted with Chinese populations (Beijing, Bio-X in Shanghai and Taiwan) were also included in our meta-analysis16222324.…”