精神分裂症是困扰人类的重大精神疾病之一，且具有很强的遗传性。近年来，随着全基因组关联性分析（Genome-wideassociationstudy,GWAS）的逐步开展，人们已经报道了一系列的精神分裂症易感基因。ZNF804A是最近首先在欧洲人群中通过病例-对照研究发现的一个精神分裂症易感基因。然而，随后在中国人群中的验证研究却报道了不一致的结果。为了探究ZNF804A在中国人群中是否是精神分裂症的易感基因，昆明动物研究所宿兵研究员的实验室（博士研究生李明）通过与云南省精神病医院和玉溪市第二人民医院合作，对这两个地区的2207份病例-对照样本进行了系统的遗传学分析。
研究发现，在欧洲人群中报道的ZNF804A的一个同精神分裂症显著相关的序列多态位点（rs1344706）在研究的云南样本中并不与精神分裂症相关。但是，他们在前人没有关注的ZNF804A基因调控区却发现了两个新的相关位点（rs359895和rs1021042）。进一步的功能实验证明，在rs359895位点的序列突变会增强ZNF804A基因调控区同广谱转录因子Sp1的结合力，从而上调ZNF804A的转录。这一结果同临床上报道的精神分裂症病人大脑中ZNF804A表达升高的现象是一致的。他们的研究发现了一个新的ZNF804A功能突变。这个突变可能是中国人群中导致精神分裂症发生的重要遗传因素之一。该研究结果发表于国际精神病学著名刊物《AmericanJournalofPsychiatry》（刊物影响因子，12.76）（生物谷 Bioon.com）
doi:10.1176/appi.ajp.2011.11030381
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Allelic Differences Between Han Chinese and Europeans for Functional Variants in ZNF804A and Their Association With Schizophrenia
Ming Li, M.Sc., Xiong-jian Luo, Ph.D., Xiao Xiao, M.Sc., Lei Shi, M.Sc., Xing-yan Liu, M.D., Li-de Yin, M.D., Hong-bo Diao, M.D., and Bing Su, Ph.D.
Objective: ZNF804A is a schizophrenia risk gene that was recently identified by genome-wide association studies as well as subsequent replications. Although the results are consistent among studies in European populations, there have been conflicting reports in Chinese populations. The authors conducted both association and functional analyses to test whether ZNF804A is a risk gene for schizophrenia in Chinese populations. Method: The authors recruited two case-control samples of independent Han Chinese (a total of 2,207 participants) from southwestern China. A total of six single-nucleotide polymorphisms (SNPs), including the key SNP (rs1344706) that showed significant association with schizophrenia in European populations and the other five promoter SNPs of ZNF804A, were tested. Based on the results of the association analysis, the authors performed two functional assays to test the impact of the risk SNP on transcriptional factor binding affinity and promoter activity. Results: The SNP rs1344706 was not associated with schizophrenia in either of the two Han Chinese groups, and this result was confirmed by meta-analyses in five Han Chinese samples. However, the authors identified two ZNF804A promoter SNPs that were significantly associated with schizophrenia in both samples, and the significance was strengthened in the combined samples and further supported by haplotype analysis. The functional assays demonstrated that the risk SNP (rs359895) can influence Sp1 binding affinity, resulting in a higher promoter activity of the risk allele. Conclusions: Our results suggest that ZNF804A is a common risk gene for schizophrenia in world populations and that the newly identified functional SNP (rs359895) is likely a risk SNP for schizophrenia.
