ZNF804A and schizophrenia susceptibility in Asian populations
ZNF804A and schizophrenia susceptibility in Asian populations
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ZNF804A 与亚洲人群的精神分裂症易感性
DOI：
10.1002/ajmg.b.32084
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发表时间：
2012-10-01
影响因子：
2.8
通讯作者：
Su, Bing
中科院分区：
文献类型：
--
作者：
Li, Ming;Shi, Cui-Juan;Su, Bing
ZNF 804 A是最近发现的精神分裂症的危险基因，已被广泛研究，该基因座的主要发现是与欧洲血统人群中的SNP rs 1344706相关。然而，在亚洲人群中，仅对rs 1344706进行了少数研究，结果不一致。在这里，我们在多个亚洲病例对照样本（10个中国人和2个日本人样本; N = 21，062）中研究了rs 1344706和精神分裂症易感性，Meta分析表明rs 1344706与精神分裂症无显著相关性（P = 0.26），表明在欧洲样本中鉴定的相同SNP在亚洲人中不是易感风险。对一组跨越ZNF 804 A整个基因组区域（520 kb）的SNP进行进一步的基因分型和关联分析，发现除了SNP rs359895（P = 7.8 × 10−5，N = 5，172）之外没有关联，SNP rs359895是一种新报道的位于ZNF 804 A启动子区域的具有功能意义的风险SNP。这表明ZNF 804 A也可能与亚洲人的精神分裂症易感性有关，尽管风险SNP与欧洲人不同，并且与正常对照相比，中国精神分裂症患者血细胞中检测到的ZNF 804 A mRNA表达上调支持了这一点（P = 0.004）。此外，使用HapMap数据进行的连锁不平衡（LD）结构分析表明，中国人和欧洲人之间ZNF 804 A上存在不同的LD区块，这可能解释了他们之间不同的关联模式，也突出了在研究多种族人群时，复杂疾病如精神分裂症的遗传研究的复杂困难。© 2012 Wiley Periodicals，Inc.
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 × 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. © 2012 Wiley Periodicals, Inc.