Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298-0032, USA.
Pharmacogenomics J. 2012 Aug;12(4):342-8. doi: 10.1038/tpj.2011.10. Epub 2011 Apr 5.
We introduce a method for detecting variants in several genes of related function with small effect on a phenotype of interest. Our method uses logistic regression to test whether multiple alleles within a functional set have significantly higher than expected predictive value, even though none individually may have strong individual effects. We illustrate this method by testing seven gene sets (including 48 genes), from a study with 1350 single nucleotide polymorphisms in 130 addiction candidate genes studied in a sample of 575 alcohol dependence (AD) cases and 530 controls. We conclude that AD is related to variation in genes participating in Glutamate and γ-amino butyric acid signaling, as has been reported elsewhere, and in stress response pathways, but not with genes in several other systems implicated in other drugs of abuse.
我们介绍了一种方法，用于检测与感兴趣的表型有小效应的相关功能的多个基因中的变体。我们的方法使用逻辑回归来测试功能集中的多个等位基因是否具有明显高于预期的预测值，即使它们单独的个体效应可能不强。我们通过测试七个基因集（包括 48 个基因）来说明这种方法，这些基因集来自一项研究，该研究在 575 例酒精依赖（AD）病例和 530 例对照的 130 个成瘾候选基因中研究了 1350 个单核苷酸多态性。我们的结论是，AD 与参与谷氨酸和γ-氨基丁酸信号转导的基因的变异有关，这在其他地方也有报道，与应激反应途径有关，但与其他几种与其他滥用药物有关的系统中的基因无关。
