Sullivan P F, Lin D, Tzeng J-Y, van den Oord E, Perkins D, Stroup T S, Wagner M, Lee S, Wright F A, Zou F, Liu W, Downing A M, Lieberman J, Close S L
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA.
Mol Psychiatry. 2008 Jun;13(6):570-84. doi: 10.1038/mp.2008.25. Epub 2008 Mar 18.
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.
关于精神分裂症的遗传学，目前确切了解的还很少。全基因组关联研究的出现，被广泛期待为一种有前景的方法，用于识别与这种重要且使人衰弱的疾病相关的可重复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738例符合《精神疾病诊断与统计手册》第四版（DSM-IV）精神分裂症标准的患者（均为CATIE研究的参与者）和733名匹配的对照组进行了492,900个单核苷酸多态性（SNP）的基因分型。在对受试者和SNP进行多个质量控制步骤之后，采用逻辑回归分析来评估所有SNP与精神分裂症关联的证据。我们确定了一些有前景的SNP用于后续研究，尽管没有单个SNP或SNP的多标记组合达到全基因组统计学显著性。虽然有一些信号与先前涉及精神分裂症的基因组区域重合，但不能排除偶然性。这些数据没有提供证据表明，在中等样本量下可检测到任何基因组区域与精神分裂症有关。然而，一项针对反应表型的全基因组关联研究计划，以及将本研究中的个体表型和基因型数据纳入荟萃分析，有望最终识别出易感性和保护性变异。
