Is the conserved mammalian region of ZNF804A locus associated with schizophrenia? A population-based genetics analysis

Abstract

Recently, several genome-wide association studies (GWASs) have reproduced the significant association of the single nucleotide polymorphism (SNP) rs1344706 (located in intron 2 of the zinc finger protein 804A (ZNF804A) on chromosome 2q32.1) with schizophrenia. Bioinformatic analysis of the chromosome segment around rs1344706 suggests that a short conserved mammalian region exists approximately 3. kb downstream of rs1344706. In the present work, we studied all SNPs in this conserved mammalian region and performed genetic analyses on samples from Chinese schizophrenia patients (n = 516) and compared control subjects (n = 520). Significant association between an allele of rs13423388 and schizophrenia was found (P= 0.0012). Haplotype analysis of the three SNPs rs4666998, rs13423388, and rs56280129 showed significant associations with schizophrenia (global P= 0.00001). Furthermore, we performed a four-SNP haplotype analysis which included the SNPs from the three-SNP haplotype analysis and rs1344706 (global P= 0.0005), and found that haplotype GCCG was associated with schizophrenia (P= 0.003). In summary, the present study adds new evidence for an association between the conserved mammalian region of the ZNF804A gene and schizophrenia. Further research is needed to clarify the transcriptional regulation of ZNF804A gene and to relate this to the pathophysiology of schizophrenia. © 2011 Elsevier B.V.