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荟萃分析表明,欧洲 GWAS 确定的 ZNF804A 内风险 SNP rs1344706 与汉族人群的精神分裂症无关。

Meta-analysis indicates that the European GWAS-identified risk SNP rs1344706 within ZNF804A is not associated with schizophrenia in Han Chinese population.

机构信息

State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, People's Republic of China.

出版信息

PLoS One. 2013 Jun 12;8(6):e65780. doi: 10.1371/journal.pone.0065780. Print 2013.

Abstract

Recent genetic association studies have implicated several candidate susceptibility variants for schizophrenia among general populations. Rs1344706, an intronic SNP within ZNF804A, was identified as one of the most compelling candidate risk SNPs for schizophrenia in Europeans through genome-wide association studies (GWASs) and replications as well as large-scale meta-analyses. However, in Han Chinese, the results for rs1344706 are inconsistent, and whether rs1344706 is an authentic risk SNP for schizophrenia in Han Chinese is inconclusive. Here, we conducted a systematic meta-analysis of rs1344706 with schizophrenia in Chinese population by combining all available case-control samples (N = 12), including a total of 8,982 cases and 12,342 controls. The results of our meta-analysis were not able to confirm an association of rs1344706 A-allele with schizophrenia (p = 0.10, odds ratio = 1.06, 95% confidence interval = 0.99-1.13). Such absence of association was further confirmed by the non-superiority test (p = 0.0003), suggesting that rs1344706 is not a risk SNP for schizophrenia in Han Chinese. Detailed examinations of individual samples revealed potential sampling bias in previous replication studies in Han Chinese. The absence of rs1344706 association in Han Chinese suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating genome-wide association findings of schizophrenia across different ethnic populations.

摘要

最近的遗传关联研究表明,在普通人群中,几种候选精神分裂症易感性变异体与精神分裂症有关。通过全基因组关联研究(GWAS)和复制以及大规模荟萃分析,发现 ZNF804A 内含子中的 SNP rs1344706 是欧洲精神分裂症最具说服力的候选风险 SNP 之一。然而,在中国汉族人群中,rs1344706 的结果并不一致,rs1344706 是否是汉族人群中精神分裂症的真实风险 SNP 尚无定论。在这里,我们通过合并所有可用的病例对照样本(N = 12),对中国人群中 rs1344706 与精神分裂症进行了系统的荟萃分析,包括总共 8982 例病例和 12342 例对照。荟萃分析的结果未能证实 rs1344706 A 等位基因与精神分裂症之间存在关联(p = 0.10,比值比 = 1.06,95%置信区间 = 0.99-1.13)。非优势检验进一步证实了这种无关联(p = 0.0003),表明 rs1344706 不是汉族人群精神分裂症的风险 SNP。对个体样本的详细检查表明,以前在中国汉族人群中的重复研究存在潜在的抽样偏差。在中国汉族人群中缺乏 rs1344706 关联表明,该基因座上精神分裂症易感性存在潜在的遗传异质性,也表明在不同种族人群中复制精神分裂症全基因组关联研究结果存在困难。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22be/3680487/9fd8f52c17dd/pone.0065780.g001.jpg

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