Further Investigation of the Association Between rs7341475 and rs17746501 and Schizophrenia
Further Investigation of the Association Between rs7341475 and rs17746501 and Schizophrenia
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DOI：
10.1002/ajmg.b.31093
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发表时间：
2010-09-01
影响因子：
2.8
通讯作者：
Shifman, Sagiv
中科院分区：
文献类型：
--
作者：
Ben-David, Eyal;Shifman, Sagiv
小样本量的全基因组关联研究（GWAS）在识别精神分裂症易感基因方面的统计能力有限。这一点可以通过以下事实来证明：只有在对三个不同的GWAS进行荟萃分析后，才能检测到最令人信服的关联之一。在这里，我们使用荟萃分析来研究两个单核苷酸多态性（SNP）（rs7341475和rs 17746501）之间的关联，这两个SNP先前被德系犹太人（AJ）的GWAS表明与精神分裂症相关。在初始报告中，rs7341475仅与女性相关，而rs 17746501与男性和女性均相关。我们收集了在四个GWAS中发表的两个SNP的样本的基因分型结果，以及AJ的结果。我们使用Mantel-Haenszel方法将不同样本的数据联合收割机组合。对于这两种SNP，所有样本的荟萃分析结果，包括初始报告，都没有达到全基因组显著性水平。然而，在排除AJ的数据后，rs7341475与女性精神分裂症之间的关联是显著的（P = 9.0 x 10（-3）），计算的比值比（OR）为1.11，远小于原始结果。rs 17746501与精神分裂症之间的关联在四个新样本中是显著的，当在所有样本中进行测试时，显示出异质性和非常小的影响（P = 0.016，OR = 1.06）。这些研究结果表明，这两个SNP可能对精神分裂症的风险有很小的影响，并建议需要对非常大的样本进行荟萃分析，以充分研究常见变异对精神分裂症易感性的贡献。(C)2010 Wiley-Liss，Inc.
Genome-wide association studies (GWAS) with small sample size have had limited statistical power in identifying schizophrenia susceptibility genes. This is exemplified by the fact that one of the most convincing associations was detected only after meta-analyses of three different GWAS. Here we used meta-analysis to study the association of two single-nucleotide polymorphisms (SNPs) (rs7341475 and rs17746501) previously indicated to be associated with schizophrenia by a GWAS of Ashkenazi Jews (AJ). In the initial report, rs7341475 was associated only in women, while rs17746501 was associated in both men and women. We collected genotyping results of samples published in four GWAS for the two SNPs, additional to results from AJ We used the Mantel-Haenszel method to combine the data of the different samples. For both SNPs, the results of the meta-analysis of all samples, including the initial report, did not reach a genome-wide significance level. However, the association between rs7341475 and schizophrenia in women, after excluding the data from AJ was significant (P = 9.0 x 10(-3)), with a calculated odds ratio (OR) of 1.11, much smaller than the original result. Association between rs17746501 and schizophrenia was significant in four of the new samples, showing evidence for heterogeneity and very small effect when tested across all samples (P = 0.016, OR = 1.06). These findings suggest that the two SNPs might have a small effect on schizophrenia risk and suggest that meta-analyses of very large samples are needed to adequately study the contribution of common variants to schizophrenia susceptibility. (C) 2010 Wiley-Liss, Inc.