State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
Am J Med Genet B Neuropsychiatr Genet. 2012 Oct;159B(7):794-802. doi: 10.1002/ajmg.b.32084. Epub 2012 Aug 6.
ZNF804A, a recently identified risk gene for schizophrenia, has been extensively investigated and the principle finding for this locus has been the association with SNP rs1344706 in populations of European ancestries. However, in Asian populations, only a few studies have been conducted for rs1344706 and the results were inconsistent. Here, we studied rs1344706 and schizophrenia susceptibility in multiple Asian case-control samples (10 Chinese and 2 Japanese samples; N = 21,062), and the meta-analyses indicated non-significant association of rs1344706 with schizophrenia (P = 0.26), suggesting the same SNP identified in European samples is not predisposing risk in Asians. Further genotyping and association analyses of a set of SNPs spanning the entire genomic region of ZNF804A (520 kb) identified no association except for SNP rs359895 (P = 7.8 x 10(-5) , N = 5,172), a newly reported risk SNP located in the ZNF804A promoter region with functional implications. This suggests that ZNF804A may also contribute to schizophrenia susceptibility in Asians although the risk SNP is different from that in Europeans, and it was supported by the detected up-regulation of ZNF804A mRNA expression in the blood cells of Chinese schizophrenia patients compared with normal controls (P = 0.004). Additionally, the linkage disequilibrium (LD) structure analyses using data from HapMap indicated distinct LD blocks across ZNF804A between Chinese and Europeans, which may explain the different association patterns between them, and also highlight the compounding difficulty of genetic studies of complex diseases like schizophrenia when studying multiple ethnic populations.
锌指蛋白 804A（ZNF804A）是一个最近被确定的精神分裂症风险基因，已经得到了广泛的研究，该基因座的主要发现是与欧洲血统人群中的 SNP rs1344706 相关。然而，在亚洲人群中，只有少数研究针对 rs1344706 进行了研究，结果并不一致。在这里，我们研究了 rs1344706 与多种亚洲病例对照样本（10 个中国样本和 2 个日本样本；N=21062）的精神分裂症易感性，荟萃分析表明 rs1344706 与精神分裂症无显著关联（P=0.26），这表明在欧洲样本中确定的相同 SNP 不会增加亚洲人的患病风险。进一步对跨越 ZNF804A 全基因组区域（520kb）的一组 SNP 进行基因分型和关联分析，除了位于 ZNF804A 启动子区域的 SNP rs359895（P=7.8×10(-5)，N=5172）外，没有发现其他与精神分裂症相关的 SNP，该 SNP 是一个新报道的风险 SNP，具有功能意义。这表明 ZNF804A 也可能导致亚洲人群的精神分裂症易感性，尽管风险 SNP 与欧洲人不同，并且在中国精神分裂症患者的血细胞中检测到 ZNF804A mRNA 表达的上调（P=0.004），这也支持了这一观点。此外，使用 HapMap 数据进行的连锁不平衡（LD）结构分析表明，中国和欧洲人之间的 ZNF804A 存在不同的 LD 块，这可能解释了它们之间不同的关联模式，也凸显了在研究多个种族人群时，研究复杂疾病（如精神分裂症）的遗传研究面临的复杂性。
