Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1244-7. doi: 10.1002/ajmg.b.31093.
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.
全基因组关联研究(GWAS)样本量小,在确定精神分裂症易感基因方面的统计效力有限。这一点可以从以下事实得到证明,即最有说服力的关联之一是在对三个不同的 GWAS 进行荟萃分析后才被发现。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 rs17746501)的关联,这些 SNP 先前通过对阿什肯纳兹犹太人(AJ)的 GWAS 表明与精神分裂症有关。在最初的报告中,rs7341475 仅在女性中相关,而 rs17746501 在男性和女性中均相关。我们收集了四个 GWAS 中发表的两个 SNP 的基因分型结果,此外还有 AJ 的结果。我们使用 Mantel-Haenszel 方法合并不同样本的数据。对于这两个 SNP,包括最初报告在内的所有样本的荟萃分析结果均未达到全基因组显著性水平。然而,在排除 AJ 数据后,rs7341475 与女性精神分裂症之间的关联具有统计学意义(P=9.0×10(-3)),计算出的优势比(OR)为 1.11,远小于原始结果。rs17746501 与精神分裂症的关联在四个新样本中均具有统计学意义,表明在所有样本中进行测试时存在异质性和非常小的影响(P=0.016,OR=1.06)。这些发现表明,这两个 SNP 可能对精神分裂症风险有较小的影响,并表明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。
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