Degnan James H, Lasky-Su Jessica, Raby Benjamin A, Xu Mousheng, Molony Cliona, Schadt Eric E, Lange Christoph
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
Genomics. 2008 Sep;92(3):129-33. doi: 10.1016/j.ygeno.2008.05.012. Epub 2008 Jun 30.
Expression QTL mapping by integrating genome-wide gene expression and genotype data is a promising approach to identifying functional genetic variation, but is hampered by the large number of multiple comparisons inherent in such studies. A novel approach to addressing multiple testing problems in genome-wide family-based association studies is screening candidate markers using heritability or conditional power. We apply these methods in settings in which microarray gene expression data are used as phenotypes, screening for SNPs near the expressed genes. We perform association analyses for phenotypes using a univariate approach. We also perform simulations on trios with large numbers of causal SNPs to determine the optimal number of markers to use in a screen. We demonstrate that our family-based screening approach performs well in the analysis of integrative genomic datasets and that screening using either heritability or conditional power produces similar, though not identical, results.
通过整合全基因组基因表达和基因型数据进行表达数量性状基因座(eQTL)定位是识别功能性遗传变异的一种有前途的方法,但此类研究中固有的大量多重比较阻碍了该方法的应用。在全基因组家系关联研究中解决多重检验问题的一种新方法是使用遗传力或条件检验效能筛选候选标记。我们将这些方法应用于以微阵列基因表达数据为表型的情况,筛选表达基因附近的单核苷酸多态性(SNP)。我们使用单变量方法对表型进行关联分析。我们还对具有大量因果SNP的三联体进行模拟,以确定筛选中使用的最佳标记数量。我们证明,我们基于家系的筛选方法在整合基因组数据集的分析中表现良好,并且使用遗传力或条件检验效能进行筛选会产生相似但不完全相同的结果。