Allelic Differences Between Han Chinese and Europeans for Functional Variants in ZNF804A and Their Association With Schizophrenia
Allelic Differences Between Han Chinese and Europeans for Functional Variants in ZNF804A and Their Association With Schizophrenia
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中国汉族和欧洲人 ZNF804A 功能变异的等位基因差异及其与精神分裂症的关系
DOI：
10.1176/appi.ajp.2011.11030381
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发表时间：
2011-12-01
影响因子：
17.7
通讯作者：
Su, Bing
中科院分区：
文献类型：
--
作者：
Li, Ming;Luo, Xiong-jian;Su, Bing
目的：ZNF804A 是最近通过全基因组关联研究以及随后的复制发现的精神分裂症风险基因。尽管针对欧洲人群的研究结果是一致的，但针对中国人群的研究结果却相互矛盾。作者进行了关联分析和功能分析，以测试 ZNF804A 是否是中国人群中精神分裂症的危险基因。方法：作者招募了来自中国西南部的两个独立汉族人的病例对照样本（总共 2,207 名参与者）。总共测试了 6 个单核苷酸多态性 (SNP)，包括与欧洲人群中的精神分裂症显着相关的关键 SNP (rs1344706) 以及 ZNF804A 的其他 5 个启动子 SNP。基于关联分析的结果，作者进行了两项功能测定，以测试风险 SNP 对转录因子结合亲和力和启动子活性的影响。 结果：SNP rs1344706 与两个中国汉族群体中的任何一个群体中的精神分裂症均无关，并且这一结果通过五个汉族样本的荟萃分析得到证实。然而，作者在两个样本中发现了两个与精神分裂症显着相关的 ZNF804A 启动子 SNP，并且这种显着性在组合样本中得到了加强，并得到单倍型分析的进一步支持。功能分析表明，风险 SNP (rs359895) 可以影响 Sp1 结合亲和力，导致风险等位基因的启动子活性更高。结论：我们的结果表明，ZNF804A 是世界人群中精神分裂症的常见风险基因，新发现的功能性 SNP (rs359895) 很可能是精神分裂症的风险 SNP。
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.