Genomewide association for schizophrenia in the CATIE study: results of stage 1
Genomewide association for schizophrenia in the CATIE study: results of stage 1
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DOI：
10.1038/mp.2008.25
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发表时间：
2008-06-01
影响因子：
11
通讯作者：
Close, S. L.
中科院分区：
文献类型：
--
作者：
Sullivan, P. F.;Lin, D.;Close, S. L.
人们对于精神分裂症的遗传学知之甚少。人们普遍预计全基因组关联的出现是一种有前途的方法，可以识别与这种重要且令人衰弱的疾病相关的可重复的 DNA 序列变异。使用 Affymetrix 500K 双芯片基因分型平台加上定制的 164K 填充芯片，对总共 738 例 DSM-IV 精神分裂症病例（CATIE 研究的所有参与者）和 733 例组匹配对照进行了 492 900 个单核苷酸多态性 (SNP) 的基因分型。对受试者和 SNP 进行多重质量控制步骤后，使用逻辑回归分析来评估所有 SNP 与精神分裂症相关的证据。我们确定了许多有前途的 SNP 用于后续研究，尽管没有 SNP 或 SNP 的多标记组合达到全基因组统计显着性。尽管一些信号与先前与精神分裂症有关的基因组区域一致，但不能排除偶然性。这些数据没有提供任何基因组区域与中等样本量可检测到的精神分裂症有关的证据。然而，一项计划中的反应表型全基因组关联研究以及将本研究中的个体表型和基因型数据纳入荟萃分析有望最终识别易感性和保护性变异。
Little is known for certain about the genetics of schizophrenia. The advent of genomewide association has been widely anticipated as a promising means to identify reproducible DNA sequence variation associated with this important and debilitating disorder. A total of 738 cases with DSM-IV schizophrenia (all participants in the CATIE study) and 733 group-matched controls were genotyped for 492 900 single-nucleotide polymorphisms (SNPs) using the Affymetrix 500K two-chip genotyping platform plus a custom 164K fill-in chip. Following multiple quality control steps for both subjects and SNPs, logistic regression analyses were used to assess the evidence for association of all SNPs with schizophrenia. We identified a number of promising SNPs for follow-up studies, although no SNP or multimarker combination of SNPs achieved genomewide statistical significance. Although a few signals coincided with genomic regions previously implicated in schizophrenia, chance could not be excluded. These data do not provide evidence for the involvement of any genomic region with schizophrenia detectable with moderate sample size. However, a planned genomewide association study for response phenotypes and inclusion of individual phenotype and genotype data from this study in meta-analyses hold promise for eventual identification of susceptibility and protective variants.