ZNF804A Genetic Variation Confers Risk to Bipolar Disorder

Abstract

Genetic variation in the gene encoding zinc finger protein 804A gene (ZNF804A) has been identified to be associated with bipolar disorder in genome-wide association studies, while little is known regarding their association in Asian populations. In this study, we aimed to examine whether ZNF804A may confer susceptibility to BD in Han Chinese. We measured the mRNA expression level of ZNF804A in patients with BD and controls. Two functional variants (rs1344706 and rs359895) in ZNF804A were genotyped among 1508 individuals with or without BD. We then performed a meta-analysis based on present literature. Our results showed that ZNF804A mRNA level in peripheral blood mononuclear cells was significantly higher in BD patients than that in controls (P = 0.01). The rs1344706 showed significant allelic association with BD (P = 0.034). The frequency of T allele of rs1344706 was higher in patients than that in controls (odds ratio = 1.19, 95 % confidence interval 1.03-1.37). After pooling all data, meta-analysis indicated a significant association of rs1344706 with BD (P = 0.0003). Furthermore, we performed an eQTL analysis and observed significant associations between rs1344706 and ZNF804A expression level in hippocampus (P = 0.032) and occipital cortex (P = 0.036). After stratified by diagnosis, the association of rs1344706 with BD was only survived in BD-I (genotypic P = 0.04, allelic P = 0.014), but not in BD-II. Our findings provided supportive evidence for the involvement of ZNF804A rs1344706 in BD, especially in BD-I.

Keywords: Bipolar disorder; Han Chinese; Subtype; ZNF804A; eQTL.